{"gene":"SOX11","run_date":"2026-06-10T07:46:38","timeline":{"discoveries":[{"year":2008,"finding":"The C-terminal 33 residues of SOX11 constitute its transactivation domain (TAD). SOX11 activates transcription more efficiently than SOX4 and SOX12, owing to a more stable alpha-helical structure of its TAD. Acidic domains and the TAD itself interfere with DNA binding.","method":"Reporter gene transactivation assays, domain mapping, structural analysis of TAD","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reporter assays with domain mutagenesis, multiple orthogonal approaches (reporter gene assays + structural analysis), single lab","pmids":["18403418"],"is_preprint":false},{"year":2020,"finding":"Cryo-EM structures show that SOX11 HMG domain binds nucleosomal DNA at superhelical location 2, locally distorting DNA and facilitating detachment of terminal nucleosomal DNA from the histone octamer, thereby increasing DNA accessibility. SOX11 binding also repositions the N-terminal tail of histone H4 including K16.","method":"Cryo-electron microscopy structure determination","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structural determination at high resolution with functional validation, published in Nature","pmids":["32350470"],"is_preprint":false},{"year":2006,"finding":"SOX11 is required for neuron survival and neurite outgrowth. siRNA-mediated knockdown in Neuro2a cells increased apoptosis and decreased neurite growth, upregulated pro-apoptotic BNIP3, and decreased anti-apoptotic TANK. In primary DRG neurons, SOX11 knockdown decreased neurite growth/branching and reduced Arpc3 (actin organizing protein) mRNA.","method":"RNAi knockdown in Neuro2a cells and primary DRG neurons, gene expression analysis","journal":"Neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined cellular phenotype and target gene identification, single lab, two cell models","pmids":["17055661"],"is_preprint":false},{"year":2008,"finding":"In vivo siRNA-mediated knockdown of Sox11 in injured mouse saphenous nerve transiently inhibited peripheral nerve regeneration of both myelinated and unmyelinated axons. Sox11 knockdown reduced ATF3 expression at transcriptional and translational levels in injured neurons.","method":"In vivo siRNA injection via Penetratin conjugation, electron microscopy, immunostaining","journal":"Brain research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo loss-of-function with morphological and molecular readouts, single lab, two orthogonal methods","pmids":["19133245"],"is_preprint":false},{"year":2013,"finding":"SOX11 promotes tumor growth in MCL xenograft models. By ChIP-microarray combined with gene expression profiling upon SOX11 knockdown, SOX11 directly targets PAX5. SOX11 silencing downregulates PAX5, induces BLIMP1, and promotes plasmacytic differentiation, blocking terminal B-cell differentiation.","method":"ChIP-microarray, gene expression profiling, siRNA knockdown, xenograft mouse model","journal":"Blood","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — ChIP-microarray identifies direct targets, knockdown with phenotypic rescue, xenograft model, multiple orthogonal methods","pmids":["23321250"],"is_preprint":false},{"year":2014,"finding":"SOX11 directly binds regulatory regions of CXCR4 and PTK2 (FAK), upregulating their expression in MCL cells. This activates PI3K/AKT and ERK1/2 FAK-downstream pathways, enhancing cell migration, stromal adhesion, endothelial transmigration, proliferation, and cell adhesion-mediated drug resistance.","method":"ChIP, gene expression analysis, siRNA knockdown, functional migration/adhesion assays, xenograft models, FAK/CXCR4 inhibitor treatment","journal":"Blood","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — ChIP demonstrates direct binding, multiple functional assays, in vivo xenograft validation, single lab","pmids":["28533307"],"is_preprint":false},{"year":2014,"finding":"SOX11 directly transcriptionally upregulates PDGFA in MCL cells. SOX11-positive MCL tumors had higher microvascular density and angiogenic gene signatures; conditioned media from SOX11+ cells promoted endothelial cell proliferation, migration, and tube formation. PDGFA inhibition impaired SOX11-enhanced angiogenesis.","method":"ChIP, gene expression profiling, conditioned media assays, endothelial cell functional assays, xenograft models with imatinib treatment","journal":"Blood","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — ChIP demonstrates direct SOX11-PDGFA regulation, multiple orthogonal functional assays, in vivo validation","pmids":["25092176"],"is_preprint":false},{"year":2010,"finding":"SOX11 directly reduces tumor growth in hematopoietic malignancies. siRNA knockdown and ectopic overexpression alter proliferation. Gene expression analysis identified Rb-E2F cell cycle regulatory pathways as associated with SOX11-induced growth reduction. SOX11 is epigenetically silenced by DNA methylation in B-cell lymphomas.","method":"siRNA knockdown, ectopic overexpression, GeneChip expression analysis, promoter methylation analysis","journal":"Molecular cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — both loss- and gain-of-function with pathway identification, single lab, multiple orthogonal approaches","pmids":["20624318"],"is_preprint":false},{"year":2011,"finding":"SOX11 epigenetic activation in aggressive B-cell lymphomas is mediated by a shift from inactivating histone marks (H3K9me2, H3K27me3) to activating histone marks (H3K9/14Ac, H3K4me3). SOX11 silencing in non-expressing lymphoid cells correlates with H3K27me3. HDAC inhibitor SAHA reversed SOX11 silencing but DNA methyltransferase inhibitor AZA did not.","method":"ChIP, bisulfite sequencing, HDAC inhibitor and DNA methyltransferase inhibitor treatment","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP for histone marks, pharmacological intervention, single lab, multiple cell types examined","pmids":["21738649"],"is_preprint":false},{"year":2011,"finding":"Sox11 knockout mice show severe reduction in sensory neuron survival in trigeminal and dorsal root ganglia, and arrest of axonal outgrowth in vivo and in vitro. This axonal growth defect could not be fully rescued by blocking cell death, indicating a cell-death-independent role in axon growth.","method":"Sox11 knockout mouse (knockin of LacZ replacing Sox11 coding region), histological analysis, in vitro axon growth assay","journal":"Developmental dynamics","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic knockout model with defined cellular phenotype, rescue experiments, two orthogonal readouts","pmids":["21117150"],"is_preprint":false},{"year":2010,"finding":"In sympathetic nervous system development, Sox11 is required early for proliferation of tyrosine hydroxylase-expressing cells, while Sox4 ensures their survival at later stages. In double Sox4/Sox11 knockout mice, sympathetic ganglia remain hypoplastic due to consecutive proliferation and survival defects, leading to dysautonomia.","method":"Mouse mutagenesis (conditional knockouts), overexpression in chicken, histological analysis","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic mouse mutagenesis with epistasis, two species, defined cellular phenotype","pmids":["20147379"],"is_preprint":false},{"year":2013,"finding":"Sox11 is required for both embryonic and adult neurogenesis. Sox11 null embryos develop small, disorganized brains with transient NPC proliferation deficits. Conditional Sox11 deletion in adult NPCs blunts proliferation in the SGZ. Functional genomics identified potential downstream target genes.","method":"Sox11 conditional knockout mice (Cre-loxP), BrdU labeling, functional genomics/transcriptomics","journal":"Developmental dynamics","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic knockout with defined proliferation phenotype, multiple developmental stages examined, downstream target identification","pmids":["23483698"],"is_preprint":false},{"year":2018,"finding":"Phosphorylation of SOX11 at serine 30 promotes nuclear over cytoplasmic localization. Mass spectrometry identified 10 putative phosphorylated serine residues in SOX11. Western blot of embryonic mouse brain lysates confirmed SOX11 is post-translationally modified by phosphorylation.","method":"Mass spectrometry, phospho-mutant analysis, Western blot, subcellular localization assays","journal":"Frontiers in molecular neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mass spectrometry identification plus mutagenesis of specific residue with localization readout, single lab","pmids":["29973868"],"is_preprint":false},{"year":2021,"finding":"USP11 deubiquitinase stabilizes SOX11 protein in the developing cortex. USP11 deficiency impairs layer 6 neuron production and delays neuronal migration. Disease-associated USP11 mutant fails to stabilize SOX11. USP11 ablation reduces SOX11 protein despite induction of Sox11 mRNA, indicating post-translational regulation.","method":"Mouse Usp11 knockout, cortical analysis, co-immunoprecipitation, neuronal migration assays","journal":"Science advances","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic knockout plus substrate identification via Co-IP, disease-mutant validation, multiple phenotypic readouts, single lab","pmids":["33579706"],"is_preprint":false},{"year":2021,"finding":"SUMOylation of SOX11 at lysine 91 (K91) regulates its nuclear localization and function. Non-SUMOylatable SOX11-K91A shows increased nuclear localization and enhanced RGC differentiation in vitro, but promotes RGC death and stronger axon regeneration after optic nerve injury in vivo. RNA-seq showed Sox11 and Sox11K91A increase axon growth gene expression but downregulate Spp1 and Opn4.","method":"Site-directed mutagenesis (K91A), in vitro RGC differentiation assay, optic nerve crush model in vivo, RNA-seq","journal":"eNeuro","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — mutagenesis of specific PTM site with subcellular localization and functional consequences both in vitro and in vivo, transcriptomic analysis","pmids":["33441400"],"is_preprint":false},{"year":2012,"finding":"Sox11 modulates BDNF transcription in an exon promoter-specific manner. Sox11 activates BDNF exon I and IV promoters via Sox binding motif 5'-AACAAAG-3'; mutation of these sites reduces activation. Sox11 overexpression in Neuro2a cells elevated exon IV and VII BDNF transcripts.","method":"Luciferase reporter assays, Sox binding site mutagenesis, RT-PCR expression analysis","journal":"Journal of neuroscience research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — reporter assay with mutagenesis validation, single lab, focused on transcriptional mechanism","pmids":["22331573"],"is_preprint":false},{"year":2012,"finding":"SOX11 and WT1 synergistically regulate the Wnt4 promoter in embryonic kidney mesenchyme. Sox11 and WT1 co-immunoprecipitate from embryonic kidney cells. Dominant negative WT1 mutants (P129L, F154S) that cannot interact with Sox11 cannot activate Wnt4. Morpholino knockdown of wt1 or sox11 in Xenopus inhibited Wnt4 expression in the pronephros.","method":"Co-immunoprecipitation, luciferase reporter assay, dominant-negative mutants, morpholino knockdown in Xenopus","journal":"Experimental cell research","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — Co-IP demonstrates protein complex, reporter assays with dominant negatives, in vivo morpholino validation, multiple orthogonal methods","pmids":["22465478"],"is_preprint":false},{"year":2013,"finding":"SOX11 directly binds conserved SOX family binding sites in the 5' UTR of GDF5 and activates GDF5 expression. SOX11 overexpression in chick limb micromass cultures directly activates GDF5, and enhances Gdf5 expression in developing chick limbs.","method":"In vitro reporter assay, micromass cultures, RCAS virus-mediated overexpression in chick limb, binding site analysis","journal":"BMC developmental biology","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — direct binding to promoter demonstrated, multiple model systems, single lab","pmids":["23356643"],"is_preprint":false},{"year":2018,"finding":"SOX11 expression in MCL is regulated by CCND1 and STAT3. CCND1 increases SOX11 transcription by sequestering HDAC1 and HDAC2 from the SOX11 locus, leading to increased H3K9/14 acetylation. STAT3 activation decreases SOX11 expression; JAK1/JAK2 inhibition or STAT3 knockdown increases SOX11 expression.","method":"ChIP, Co-IP, RNAi knockdown, ectopic overexpression, HDAC inhibitor treatment, cytokine stimulation assays","journal":"Blood","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — ChIP demonstrates HDAC displacement from SOX11 locus, Co-IP shows CCND1-HDAC interaction, multiple orthogonal mechanistic approaches, single lab","pmids":["30530749"],"is_preprint":false},{"year":2018,"finding":"SOX11 overexpression in B cells drives BCR signaling hyperactivation (pBTK and downstream molecules) and produces an oligoclonal B-cell hyperplasia with MCL-like immunophenotype (CD5+CD19+CD23-). Serial bone marrow transplant from transgenic donors produces lethal disease with decreasing latency.","method":"Transgenic mouse model (Eμ-SOX11-EGFP), phosphocytometric mass cytometry (CyTOF), bone marrow transplantation","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Moderate — transgenic mouse model with defined signaling phenotype, transplantation experiments confirming tumorigenicity, single lab","pmids":["29615403"],"is_preprint":false},{"year":2016,"finding":"Sox11 suppresses dendritic morphogenesis of excitatory neurons in mouse cerebral cortex. Loss-of-function causes precocious neurite branching and a neuronal migration defect; gain-of-function inhibits dendritic morphogenesis. Arrival at final cortical position induces Sox11 downregulation, which is required to permit dendritic branching.","method":"In utero electroporation and postnatal electroporation (loss- and gain-of-function), morphological analysis","journal":"The Journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — both loss- and gain-of-function with defined cellular phenotype, single lab, in vivo model","pmids":["27225767"],"is_preprint":false},{"year":2019,"finding":"SOX11 and SOX4 regulate embryonic epidermal state and are required for wound re-epithelialization. They regulate cytoskeletal/ECM genes and directly target FSCN1 (fascin), which mediates cell migration. Sox11/Sox4 deficiency accelerates differentiation and dramatically impairs cell motility.","method":"Mouse knockout models, chromatin immunoprecipitation, gene expression profiling, wound healing assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — genetic knockouts, ChIP demonstrating direct target, multiple functional readouts, single lab","pmids":["31492871"],"is_preprint":false},{"year":2014,"finding":"Sox11 overexpression in MSCs transcriptionally activates Runx2 and CXCR4 expression (demonstrated by dual-luciferase reporter assay) and activates the BMP/Smad signaling pathway, enhancing trilineage differentiation and migration of MSCs.","method":"Lentiviral overexpression, dual-luciferase reporter assay, ectopic bone formation, western blot, open fracture rat model","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — reporter assay for direct transcriptional targets, multiple differentiation assays, in vivo model, single lab","pmids":["25466891"],"is_preprint":false},{"year":2020,"finding":"Wnt7b induces Sox11 expression in BMSCs via a β-catenin-independent, Ca2+-dependent Nfatc1 signaling pathway. ChIP-qPCR showed Nfatc1 directly binds the Sox11 promoter. Sox11 in turn transcriptionally activates Ccnb1, Sox2 (proliferation) and Runx2, Sp7 (osteogenesis).","method":"ChIP-qPCR, RNA-seq, shRNA knockdown, transgenic mice, immunofluorescence, ex vivo transplantation","journal":"Stem cells (Dayton, Ohio)","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — ChIP demonstrates Nfatc1-Sox11 promoter binding, multiple downstream targets identified, single lab","pmids":["32346881"],"is_preprint":false},{"year":2021,"finding":"SOX11 directly upregulates CD70 expression in MCL cells. CD70 overexpression in SOX11+ MCL is associated with increased Treg cell infiltration and an immunosuppressive tumor microenvironment. CD40L stimulation induces CD70 in SOX11+ but not SOX11- MCL cells in vitro.","method":"ChIP (binding to CD70 regulatory regions), gene expression analysis, immunohistochemistry, in vitro stimulation assays","journal":"Blood","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP demonstrates direct SOX11-CD70 regulation, multiple validation approaches, single lab","pmids":["34189576"],"is_preprint":false},{"year":2009,"finding":"Sox11 overexpression in glioma-initiating cells (NSC-derived) prevents tumorigenesis by inducing neuronal differentiation, accompanied by decreased plagl1 expression. Plagl1 overexpression abolishes neuronal commitment and induces tumorigenicity. Sox11 loss is found in human glioma-initiating cells, and Sox11 overexpression prevents their tumorigenesis in vivo.","method":"Gene expression profiling, overexpression assays, in vivo tumorigenesis, limiting dilution assays","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain-of-function with in vivo tumorigenesis readout, epistasis with plagl1, single lab","pmids":["19808959"],"is_preprint":false},{"year":2017,"finding":"Endogenous SOX11 directly binds the SDCCAG8 gene promoter in highly invasive HNSCC cells. Wild-type SOX11 but not a DNA-binding mutant activates SDCCAG8 promoter activity. Inhibitory effects of SOX11 knockdown on proliferation, migration, and invasion were partially rescued by SDCCAG8 overexpression.","method":"ChIP, luciferase reporter assay, mutagenesis, quantitative proteomics, rescue assay","journal":"Journal of experimental & clinical cancer research","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — ChIP and reporter assay with mutagenesis demonstrate direct target regulation, rescue assay validates pathway, single lab","pmids":["30922366"],"is_preprint":false},{"year":2017,"finding":"SOX11 binds the slug (SNAI2) promoter and activates its transcription in MCF-7 tamoxifen-resistant breast cancer cells, promoting epithelial-to-mesenchymal transition and suppressing ESR1 expression.","method":"Chromatin immunoprecipitation, luciferase reporter assay, gene expression analysis","journal":"Journal of cellular physiology","confidence":"Medium","confidence_rationale":"Tier 1-2 / Weak — ChIP and reporter assay demonstrate direct transcriptional regulation, single lab, single model","pmids":["32043610"],"is_preprint":false},{"year":2023,"finding":"SOX11 is a core regulatory circuitry (CRC) transcription factor in adrenergic neuroblastoma. SOX11 directly regulates 10 SWI/SNF core components (including SMARCC1, SMARCA4/BRG1, ARID1A), HDAC2, PRC1 component CBX2, KDM1A/LSD1, and c-MYB. SOX11 is regulated by multiple adrenergic-specific super-enhancers.","method":"ChIP-seq, enhancer analysis, gene expression dependency analysis, neuroblastoma cell line functional studies","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — ChIP-seq demonstrates direct binding and regulation of chromatin regulatory complex components, super-enhancer analysis, multiple orthogonal approaches","pmids":["36882421"],"is_preprint":false},{"year":2017,"finding":"SOX11 binds to HSP90α (HSP90AA1) in head and neck cancer cells. The interaction was identified by Co-IP/LC-MS/MS and validated by Co-IP with western blotting.","method":"Co-immunoprecipitation, liquid chromatography-tandem mass spectrometry (LC-MS/MS), western blotting","journal":"Journal of proteome research","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — Co-IP/MS identification validated by reciprocal Co-IP, single lab, functional consequence of interaction not directly established","pmids":["28915052"],"is_preprint":false},{"year":2018,"finding":"SOX11 overexpression in HCC cells enhances nemo-like kinase expression and TCF4 phosphorylation, thereby inhibiting Wnt/β-catenin signaling and promoting growth inhibition and apoptosis.","method":"Overexpression assays, western blot, cell viability and apoptosis assays","journal":"Biotechnology and applied biochemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single overexpression system, signaling pathway changes by western blot, single lab, limited mechanistic depth","pmids":["30517979"],"is_preprint":false},{"year":2013,"finding":"Cell-type-specific deletion shows Sox11 is required for proper outflow tract development in both mesodermal cells and neural crest cells. Sox4 and Sox11 become essential after neural crest arrival in the outflow tract for differentiation and interaction through regulation of cytoskeletal, cell adhesion, and ECM molecules.","method":"Cell-type-specific conditional deletion in mouse (mesoderm and neural crest), phenotypic analysis","journal":"Cellular and molecular life sciences","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with cell-type-specific deletion, defined phenotypic readouts, molecular pathway identification","pmids":["24310815"],"is_preprint":false},{"year":2018,"finding":"Sox11 disruption in mice causes CAKUT including duplex kidney formation. SOX11 directly binds and regulates a locus control region of the protocadherin B cluster. SOX11 regulates elongation of Henle's loop. A CAKUT-associated SOX11 variant identified in patients interferes with SOX11 transactivation capacity.","method":"Sox11 knockout mouse, ChIP demonstrating direct binding to protocadherin B locus control region, transactivation assays","journal":"Kidney international","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — genetic knockout with defined developmental phenotype, ChIP demonstrates direct binding, human variant functional analysis, single lab","pmids":["29459093"],"is_preprint":false},{"year":2016,"finding":"Sox11 deficiency causes cleft palate through mandibular hypoplasia; Sox11 loss reduces cell proliferation in mandibular mesenchyme via Cyclin D1. In vitro assays show Sox11 directly regulates Fgf9 expression, and FGF9 protein application to Sox11-deficient palatal shelves restores BrdU incorporation.","method":"Sox11 knockout mouse, BrdU proliferation assay, gene expression analysis, in vitro FGF9 rescue assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic knockout with phenotypic analysis, direct target (Fgf9) validated by rescue assay, single lab","pmids":["26826126"],"is_preprint":false},{"year":2019,"finding":"SOX11 promotes cell migration in wounded skin by activating expression of FSCN1 (fascin actin-bundling protein 1) as a direct transcriptional target. Sox11/Sox4 deficiency impairs cell motility and re-epithelialization.","method":"ChIP, mouse knockout models, wound healing assays, gene expression profiling","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — ChIP demonstrates direct SOX11-FSCN1 regulation, genetic knockouts with functional phenotype, single lab","pmids":["31492871"],"is_preprint":false},{"year":2017,"finding":"LHX2 binds distal regulatory elements of Sox11 in cortical progenitors and interacts with NuRD complex subunits LSD1, HDAC2, and RBBP4 to maintain repressive chromatin at the Sox11 locus. Loss of LHX2 increases active histone marks at Sox11 loci and increases Sox11 expression, while LHX2 overexpression decreases it.","method":"ChIP, Co-IP (LHX2 with NuRD complex components), conditional knockout, overexpression, histone mark analysis","journal":"The Journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP demonstrates direct binding, Co-IP shows protein complex, genetic manipulation with molecular readout, single lab","pmids":["28053041"],"is_preprint":false},{"year":2022,"finding":"LINC01296 binds nucleolin (NCL) and forms a complex that activates SOX11 gene transcription, promoting neuroblastoma tumorigenesis. Silencing LINC01296 reduces SOX11 expression; RNA pull-down validated the LINC01296-NCL interaction.","method":"RNA pull-down assay, Co-IP, luciferase reporter assay, siRNA knockdown, in vivo xenograft","journal":"Molecular therapy oncolytics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNA pull-down validates lncRNA-protein interaction, downstream SOX11 transcriptional activation demonstrated, in vivo validation, single lab","pmids":["35317520"],"is_preprint":false},{"year":2019,"finding":"Sox11 in spinal cord injury promotes neuronal differentiation of endogenous neural stem cells and induces BDNF expression in the injured cord, improving locomotor recovery.","method":"Lentiviral Sox11 delivery to injured mouse spinal cord, immunostaining, behavioral assays","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — gain-of-function in vivo with cellular and behavioral readouts, molecular mechanism not deeply probed, single lab","pmids":["24589730"],"is_preprint":false},{"year":2020,"finding":"SOX11 confers a hybrid epithelial/mesenchymal (E/M) state in ER-negative breast cancer cells, leading to alterations in metastatic tropism (increased brain and bone metastasis, decreased lung metastasis) in xenograft models.","method":"SOX11 overexpression in DCIS.com cells, xenograft mouse model, single-cell analysis, E/M marker analysis","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain-of-function with defined in vivo metastatic phenotype, single lab, molecular characterization","pmids":["32909943"],"is_preprint":false},{"year":2015,"finding":"SOX11 promoter in non-malignant cells shows low methylation with strong H3K27me3 enrichment. In cancer cells with low SOX11 methylation, HDAC inhibitors (vorinostat, trichostatin A) can reactivate SOX11 expression, while cells with dense methylation are resistant to re-expression.","method":"Bisulfite sequencing, ChIP-qPCR for H3K27me3, HDAC inhibitor treatment, methylation assays in 42 cell lines","journal":"BMC cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP and methylation analysis across multiple cell lines with pharmacological validation, single lab","pmids":["25880212"],"is_preprint":false},{"year":2019,"finding":"SOX11 transcriptionally activates β-catenin expression in MSCs (core promoter region -242 to -1414 identified). Sox11 also interacts with β-catenin protein (co-immunoprecipitation) suggesting post-transcriptional regulation in addition to transcriptional activation.","method":"Dual-luciferase reporter assay, co-immunoprecipitation, quantitative RT-PCR, in vivo cartilage defect model","journal":"Cell and tissue research","confidence":"Medium","confidence_rationale":"Tier 1-2 / Weak — reporter assay defines promoter region, Co-IP shows protein interaction, single lab, single model system","pmids":["30617615"],"is_preprint":false}],"current_model":"SOX11 is a SOXC-group HMG-box transcription factor that acts as a pioneer factor, binding nucleosomal DNA at superhelical location 2 to locally distort DNA and increase chromatin accessibility; its transactivation domain (C-terminal 33 residues with a stable alpha-helical structure) drives target gene expression, while its activity and subcellular localization are regulated by post-translational modifications including phosphorylation at S30 (promoting nuclear localization) and SUMOylation at K91 (restricting nuclear localization); upstream regulators include CCND1 (which sequesters HDAC1/2 from the SOX11 locus to increase histone acetylation), STAT3 (which represses SOX11), USP11 deubiquitinase (which stabilizes SOX11 protein), and Wnt7b/Nfatc1 signaling; in neural development SOX11 promotes neuron survival, axon growth, and maturation while suppressing premature dendritic branching; in lymphoma, SOX11 drives MCL pathogenesis by blocking terminal B-cell differentiation through direct transcriptional activation of PAX5, promoting tumor angiogenesis via PDGFA, and enhancing BCR signaling and microenvironment interactions through CXCR4 and FAK; in other contexts SOX11 directly regulates GDF5, Wnt4, FSCN1, BDNF, Runx2, CXCR4, CD70, SDCCAG8, and SWI/SNF complex components including SMARCA4/BRG1."},"narrative":{"mechanistic_narrative":"SOX11 is an HMG-box transcription factor that functions as a pioneer factor and master regulator across neural development, tissue morphogenesis, and oncogenesis [PMID:32350470, PMID:23321250]. Structurally, its HMG domain engages nucleosomal DNA at superhelical location 2 to locally distort DNA, detach terminal nucleosomal DNA from the histone octamer, and reposition the histone H4 N-terminal tail, thereby increasing chromatin accessibility, while a C-terminal transactivation domain with a stable alpha-helical structure drives target gene expression more efficiently than its SOXC paralogs [PMID:32350470, PMID:18403418]. Its activity and nuclear localization are tuned by post-translational modification: phosphorylation at S30 promotes nuclear localization, SUMOylation at K91 restricts nuclear localization and constrains axon-growth programs, and the deubiquitinase USP11 stabilizes SOX11 protein to support cortical neuron production [PMID:29973868, PMID:33441400, PMID:33579706]. In neural development SOX11 is required for neuron survival, proliferation of neural progenitors, and axon growth in both embryonic and adult contexts, while its downregulation upon neuronal maturation is required to permit dendritic branching [PMID:21117150, PMID:23483698, PMID:27225767]. SOX11 governs morphogenesis of multiple tissues through direct transcriptional targets, including FSCN1 in epidermal wound re-epithelialization, GDF5 in limb, Fgf9 in palate, and a protocadherin B locus control region in kidney; a CAKUT-associated SOX11 variant impairing transactivation links SOX11 to congenital kidney malformation in patients [PMID:31492871, PMID:23356643, PMID:26826126, PMID:29459093]. In mantle cell lymphoma SOX11 drives pathogenesis by blocking terminal B-cell differentiation through direct activation of PAX5, promoting angiogenesis via PDGFA, and enhancing BCR signaling, stromal interactions and immune evasion through CXCR4, PTK2/FAK, and CD70; its own expression is set epigenetically by a shift from repressive to activating histone marks and by CCND1-mediated displacement of HDAC1/2 from the SOX11 locus [PMID:23321250, PMID:25092176, PMID:28533307, PMID:34189576, PMID:30530749, PMID:21738649]. SOX11 also acts as a core regulatory circuitry factor in adrenergic neuroblastoma, directly regulating SWI/SNF, NuRD, and PRC1 chromatin-machinery components [PMID:36882421].","teleology":[{"year":2006,"claim":"Established that SOX11 is functionally required in neurons, not merely expressed there, by showing its loss kills neurons and stunts neurite growth.","evidence":"RNAi knockdown in Neuro2a and primary DRG neurons with apoptosis and neurite readouts","pmids":["17055661"],"confidence":"Medium","gaps":["Direct transcriptional targets driving survival vs. growth not separated","Cell-autonomy in vivo not addressed"]},{"year":2008,"claim":"Defined the structural basis of SOX11's transactivation by mapping the C-terminal TAD and explaining why SOX11 activates more strongly than its SOXC paralogs.","evidence":"Reporter transactivation assays, domain mapping, and TAD structural analysis","pmids":["18403418"],"confidence":"High","gaps":["Coactivators recruited by the TAD not identified","Regulation of TAD/DNA-binding interference in cells unresolved"]},{"year":2010,"claim":"Distinguished SOX11 from SOX4 functionally within the SOXC group, showing SOX11 drives early progenitor proliferation while SOX4 supports later survival.","evidence":"Conditional and double Sox4/Sox11 knockout mice plus chicken overexpression in sympathetic ganglia","pmids":["20147379"],"confidence":"High","gaps":["Target genes mediating proliferation vs. survival not defined","Mechanism of paralog functional divergence unknown"]},{"year":2011,"claim":"Separated SOX11's survival and axon-growth functions genetically, proving a cell-death-independent role in axon outgrowth.","evidence":"Sox11 LacZ-knockin knockout mouse with histology and in vitro axon growth, including cell-death blockade","pmids":["21117150"],"confidence":"High","gaps":["Direct axon-growth target genes not identified","How axon vs. survival programs are partitioned unclear"]},{"year":2013,"claim":"Identified the central oncogenic mechanism in MCL: SOX11 directly activates PAX5 to enforce a B-cell program and block plasmacytic differentiation.","evidence":"ChIP-microarray, expression profiling, siRNA knockdown, and MCL xenografts","pmids":["23321250"],"confidence":"High","gaps":["Full direct target network beyond PAX5 not mapped","Cofactors at the PAX5 locus unknown"]},{"year":2014,"claim":"Explained how SOX11 reshapes the MCL microenvironment by directly activating PDGFA (angiogenesis) and CXCR4/PTK2-FAK (migration, adhesion, drug resistance).","evidence":"ChIP, functional migration/adhesion/angiogenesis assays, and xenografts with inhibitor treatment","pmids":["25092176","28533307"],"confidence":"High","gaps":["Relative contribution of each target to tumor growth not quantified","Direct vs. paracrine effects partly entangled"]},{"year":2018,"claim":"Resolved how SOX11 expression is set in MCL, showing CCND1 displaces HDAC1/2 from the locus to raise histone acetylation while STAT3 represses it.","evidence":"ChIP, Co-IP, RNAi, overexpression, HDAC inhibitor and cytokine assays","pmids":["30530749"],"confidence":"High","gaps":["Transcription factors directing CCND1/HDAC to the locus unknown","Interplay with DNA methylation status not fully integrated"]},{"year":2018,"claim":"Demonstrated SOX11 is a bona fide MCL driver in vivo, sufficient to hyperactivate BCR signaling and produce MCL-like disease.","evidence":"Eu-SOX11 transgenic mouse, CyTOF signaling analysis, serial bone marrow transplantation","pmids":["29615403"],"confidence":"High","gaps":["Direct targets linking SOX11 to BTK activation not pinpointed","Cooperating lesions for full malignancy not defined"]},{"year":2018,"claim":"Extended SOX11 from neural roles to organ morphogenesis, linking it to human CAKUT and identifying direct regulation of a protocadherin B locus control region.","evidence":"Sox11 knockout mouse, ChIP, patient variant transactivation analysis","pmids":["29459093"],"confidence":"High","gaps":["Effector genes downstream of protocadherin regulation in kidney unclear","Penetrance of human variant not established"]},{"year":2019,"claim":"Established a cytoskeletal output for SOX11 by showing it, with SOX4, directly activates FSCN1 to drive cell motility in epidermal wound re-epithelialization.","evidence":"Mouse knockouts, ChIP, expression profiling, wound-healing assays","pmids":["31492871","24310815"],"confidence":"High","gaps":["Whether the same motility program operates in tumors not directly tested","Division of labor between SOX11 and SOX4 unresolved"]},{"year":2020,"claim":"Provided the structural mechanism for SOX11 pioneer activity, showing HMG-domain binding to nucleosomal DNA distorts DNA and increases accessibility.","evidence":"Cryo-EM structures of SOX11 HMG domain on nucleosomes","pmids":["32350470"],"confidence":"High","gaps":["How TAD and PTMs feed back on nucleosome engagement not shown","Genome-wide pioneer targeting rules not derived from structure"]},{"year":2021,"claim":"Defined post-translational control of SOX11 abundance and localization, with USP11 stabilizing the protein and S30 phosphorylation / K91 SUMOylation gating nuclear access and axon-growth programs.","evidence":"Usp11 knockout mouse and Co-IP; mass spectrometry and phospho/SUMO site mutants with localization and optic-nerve regeneration readouts","pmids":["33579706","29973868","33441400"],"confidence":"High","gaps":["Kinases and SUMO E3 ligases acting on SOX11 not identified","Crosstalk among phosphorylation, SUMOylation and ubiquitination unresolved"]},{"year":2023,"claim":"Positioned SOX11 atop chromatin regulation by showing it acts as a core regulatory circuitry factor directly governing SWI/SNF, NuRD and PRC1 components in adrenergic neuroblastoma.","evidence":"ChIP-seq, super-enhancer and dependency analysis in neuroblastoma cell lines","pmids":["36882421"],"confidence":"High","gaps":["Functional consequence of regulating each chromatin complex not dissected","Whether this circuitry generalizes beyond neuroblastoma unknown"]},{"year":null,"claim":"How SOX11's pioneer activity, transactivation domain, and post-translational modifications are integrated to select context-specific target gene sets across neurons, epithelia, and tumors remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No unified model linking PTM state to genomic target choice","Coactivator/corepressor complexes recruited by the TAD largely unidentified","Determinants of oncogenic vs. tumor-suppressive output across tissues unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,4,5,6,17,28,32,34]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[1,26,32]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[12,14]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,4,34]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[1,28,18]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[9,10,11,31,32,33]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[4,5,6,24]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[2,9,20]}],"complexes":[],"partners":["USP11","WT1","CCND1","HSP90AA1","CTNNB1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P35716","full_name":"Transcription factor SOX-11","aliases":[],"length_aa":441,"mass_kda":46.7,"function":"Transcription factor that acts as a transcriptional activator (PubMed:24886874, PubMed:26543203). Binds cooperatively with POU3F2/BRN2 or POU3F1/OCT6 to gene promoters, which enhances transcriptional activation (By similarity). Acts as a transcriptional activator of TEAD2 by binding to its gene promoter and first intron (By similarity). Plays a redundant role with SOX4 and SOX12 in cell survival of developing tissues such as the neural tube, branchial arches and somites, thereby contributing to organogenesis (By similarity)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/P35716/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SOX11","classification":"Not Classified","n_dependent_lines":20,"n_total_lines":1208,"dependency_fraction":0.016556291390728478},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SOX11","total_profiled":1310},"omim":[{"mim_id":"615866","title":"INTELLECTUAL DEVELOPMENTAL DISORDER WITH MICROCEPHALY AND WITH OR WITHOUT OCULAR MALFORMATIONS OR HYPOGONADOTROPIC HYPOGONADISM; IDDMOH","url":"https://www.omim.org/entry/615866"},{"mim_id":"610161","title":"TRANSCRIPTION FACTOR AP2-DELTA; TFAP2D","url":"https://www.omim.org/entry/610161"},{"mim_id":"609476","title":"NEMO-LIKE KINASE; NLK","url":"https://www.omim.org/entry/609476"},{"mim_id":"607414","title":"FEZ FAMILY ZINC FINGER PROTEIN 2; FEZF2","url":"https://www.omim.org/entry/607414"},{"mim_id":"604975","title":"SRY-BOX 5; SOX5","url":"https://www.omim.org/entry/604975"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Plasma membrane","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in single","driving_tissues":[{"tissue":"brain","ntpm":2.7}],"url":"https://www.proteinatlas.org/search/SOX11"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"P35716","domains":[{"cath_id":"1.10.30.10","chopping":"55-111","consensus_level":"high","plddt":96.3967,"start":55,"end":111}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P35716","model_url":"https://alphafold.ebi.ac.uk/files/AF-P35716-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P35716-F1-predicted_aligned_error_v6.png","plddt_mean":56.41},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SOX11","jax_strain_url":"https://www.jax.org/strain/search?query=SOX11"},"sequence":{"accession":"P35716","fasta_url":"https://rest.uniprot.org/uniprotkb/P35716.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P35716/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P35716"}},"corpus_meta":[{"pmid":"19880778","id":"PMC_19880778","title":"SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype.","date":"2009","source":"Haematologica","url":"https://pubmed.ncbi.nlm.nih.gov/19880778","citation_count":277,"is_preprint":false},{"pmid":"18403418","id":"PMC_18403418","title":"The three SoxC proteins--Sox4, Sox11 and Sox12--exhibit overlapping expression patterns and molecular properties.","date":"2008","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/18403418","citation_count":214,"is_preprint":false},{"pmid":"32350470","id":"PMC_32350470","title":"Nucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32350470","citation_count":206,"is_preprint":false},{"pmid":"19133245","id":"PMC_19133245","title":"Sox11 transcription factor modulates peripheral nerve regeneration in adult mice.","date":"2008","source":"Brain research","url":"https://pubmed.ncbi.nlm.nih.gov/19133245","citation_count":121,"is_preprint":false},{"pmid":"23321250","id":"PMC_23321250","title":"SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma.","date":"2013","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/23321250","citation_count":119,"is_preprint":false},{"pmid":"9337129","id":"PMC_9337129","title":"Expression of the Sox11 gene in mouse embryos suggests roles in neuronal maturation and epithelio-mesenchymal induction.","date":"1997","source":"Developmental dynamics : an official publication of the American Association of Anatomists","url":"https://pubmed.ncbi.nlm.nih.gov/9337129","citation_count":118,"is_preprint":false},{"pmid":"19880779","id":"PMC_19880779","title":"Strong lymphoid nuclear expression of SOX11 transcription factor defines lymphoblastic neoplasms, mantle cell lymphoma and Burkitt's lymphoma.","date":"2009","source":"Haematologica","url":"https://pubmed.ncbi.nlm.nih.gov/19880779","citation_count":117,"is_preprint":false},{"pmid":"17055661","id":"PMC_17055661","title":"SRY-box containing gene 11 (Sox11) transcription factor is required for neuron survival and neurite growth.","date":"2006","source":"Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/17055661","citation_count":115,"is_preprint":false},{"pmid":"20147379","id":"PMC_20147379","title":"Sequential requirement of Sox4 and Sox11 during development of the sympathetic nervous system.","date":"2010","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/20147379","citation_count":104,"is_preprint":false},{"pmid":"12125983","id":"PMC_12125983","title":"Differential expression of SOX4 and SOX11 in medulloblastoma.","date":"2002","source":"Journal of neuro-oncology","url":"https://pubmed.ncbi.nlm.nih.gov/12125983","citation_count":100,"is_preprint":false},{"pmid":"28533307","id":"PMC_28533307","title":"SOX11 promotes tumor protective microenvironment interactions through CXCR4 and FAK regulation in mantle cell lymphoma.","date":"2017","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/28533307","citation_count":99,"is_preprint":false},{"pmid":"19808959","id":"PMC_19808959","title":"Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.","date":"2009","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/19808959","citation_count":99,"is_preprint":false},{"pmid":"25092176","id":"PMC_25092176","title":"SOX11 promotes tumor angiogenesis through transcriptional regulation of PDGFA in mantle cell lymphoma.","date":"2014","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/25092176","citation_count":96,"is_preprint":false},{"pmid":"19490090","id":"PMC_19490090","title":"Expression of Sox11 in adult neurogenic niches suggests a stage-specific role in adult neurogenesis.","date":"2009","source":"The European journal of neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/19490090","citation_count":96,"is_preprint":false},{"pmid":"23483698","id":"PMC_23483698","title":"Transcription factor Sox11 is essential for both embryonic and adult neurogenesis.","date":"2013","source":"Developmental dynamics : an official publication of the American Association of Anatomists","url":"https://pubmed.ncbi.nlm.nih.gov/23483698","citation_count":92,"is_preprint":false},{"pmid":"32574812","id":"PMC_32574812","title":"Regulatory roles for SOX11 in development, stem cells and cancer.","date":"2020","source":"Seminars in cancer biology","url":"https://pubmed.ncbi.nlm.nih.gov/32574812","citation_count":78,"is_preprint":false},{"pmid":"8666406","id":"PMC_8666406","title":"The human SOX11 gene: cloning, chromosomal assignment and tissue expression.","date":"1995","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/8666406","citation_count":76,"is_preprint":false},{"pmid":"31492871","id":"PMC_31492871","title":"SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31492871","citation_count":74,"is_preprint":false},{"pmid":"31210798","id":"PMC_31210798","title":"SOX11: friend or foe in tumor prevention and carcinogenesis?","date":"2019","source":"Therapeutic advances in medical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/31210798","citation_count":70,"is_preprint":false},{"pmid":"28587313","id":"PMC_28587313","title":"RETRACTED: MicroRNA-223-3p Regulates Ovarian Cancer Cell Proliferation and Invasion by Targeting SOX11 Expression.","date":"2017","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/28587313","citation_count":63,"is_preprint":false},{"pmid":"25466891","id":"PMC_25466891","title":"Sox11-modified mesenchymal stem cells (MSCs) accelerate bone fracture healing: Sox11 regulates differentiation and migration of MSCs.","date":"2014","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/25466891","citation_count":62,"is_preprint":false},{"pmid":"28053041","id":"PMC_28053041","title":"LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11.","date":"2017","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/28053041","citation_count":62,"is_preprint":false},{"pmid":"20624318","id":"PMC_20624318","title":"SOX11 expression correlates to promoter methylation and regulates tumor growth in hematopoietic malignancies.","date":"2010","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/20624318","citation_count":61,"is_preprint":false},{"pmid":"22251940","id":"PMC_22251940","title":"Cyclin D1-negative blastoid mantle cell lymphoma identified by SOX11 expression.","date":"2012","source":"The American journal of surgical pathology","url":"https://pubmed.ncbi.nlm.nih.gov/22251940","citation_count":53,"is_preprint":false},{"pmid":"27225767","id":"PMC_27225767","title":"Sox11 Balances Dendritic Morphogenesis with Neuronal Migration in the Developing Cerebral Cortex.","date":"2016","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/27225767","citation_count":53,"is_preprint":false},{"pmid":"34189576","id":"PMC_34189576","title":"SOX11, CD70, and Treg cells configure the tumor-immune microenvironment of aggressive mantle cell lymphoma.","date":"2021","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/34189576","citation_count":49,"is_preprint":false},{"pmid":"21117150","id":"PMC_21117150","title":"Sox11 regulates survival and axonal growth of embryonic sensory neurons.","date":"2011","source":"Developmental dynamics : an official publication of the American Association of Anatomists","url":"https://pubmed.ncbi.nlm.nih.gov/21117150","citation_count":47,"is_preprint":false},{"pmid":"25766675","id":"PMC_25766675","title":"SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients.","date":"2015","source":"Neurobiology of disease","url":"https://pubmed.ncbi.nlm.nih.gov/25766675","citation_count":47,"is_preprint":false},{"pmid":"29738333","id":"PMC_29738333","title":"SOX11, a key oncogenic factor in mantle cell lymphoma.","date":"2018","source":"Current opinion in hematology","url":"https://pubmed.ncbi.nlm.nih.gov/29738333","citation_count":46,"is_preprint":false},{"pmid":"22642745","id":"PMC_22642745","title":"SOX11 is useful in differentiating cyclin D1-positive diffuse large B-cell lymphoma from mantle cell lymphoma.","date":"2012","source":"Histopathology","url":"https://pubmed.ncbi.nlm.nih.gov/22642745","citation_count":45,"is_preprint":false},{"pmid":"29615403","id":"PMC_29615403","title":"SOX11 augments BCR signaling to drive MCL-like tumor development.","date":"2018","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/29615403","citation_count":43,"is_preprint":false},{"pmid":"24310815","id":"PMC_24310815","title":"Cardiac outflow tract development relies on the complex function of Sox4 and Sox11 in multiple cell types.","date":"2013","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/24310815","citation_count":42,"is_preprint":false},{"pmid":"32346881","id":"PMC_32346881","title":"Wnt7b-induced Sox11 functions enhance self-renewal and osteogenic commitment of bone marrow mesenchymal stem cells.","date":"2020","source":"Stem cells (Dayton, Ohio)","url":"https://pubmed.ncbi.nlm.nih.gov/32346881","citation_count":41,"is_preprint":false},{"pmid":"29272888","id":"PMC_29272888","title":"Overexpression of SOX11 and TFE3 in Solid-Pseudopapillary Neoplasms of the Pancreas.","date":"2017","source":"American journal of clinical pathology","url":"https://pubmed.ncbi.nlm.nih.gov/29272888","citation_count":39,"is_preprint":false},{"pmid":"23356643","id":"PMC_23356643","title":"SOX11 contributes to the regulation of GDF5 in joint maintenance.","date":"2013","source":"BMC developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/23356643","citation_count":39,"is_preprint":false},{"pmid":"21738649","id":"PMC_21738649","title":"Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21738649","citation_count":38,"is_preprint":false},{"pmid":"26360498","id":"PMC_26360498","title":"Plasma cell and terminal B-cell differentiation in mantle cell lymphoma mainly occur in the SOX11-negative subtype.","date":"2015","source":"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc","url":"https://pubmed.ncbi.nlm.nih.gov/26360498","citation_count":37,"is_preprint":false},{"pmid":"29218252","id":"PMC_29218252","title":"miR-145 targets the SOX11 3'UTR to suppress endometrial cancer growth.","date":"2017","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/29218252","citation_count":37,"is_preprint":false},{"pmid":"28707729","id":"PMC_28707729","title":"SOX11 promotes invasive growth and ductal carcinoma in situ progression.","date":"2017","source":"The Journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/28707729","citation_count":36,"is_preprint":false},{"pmid":"33579706","id":"PMC_33579706","title":"Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization.","date":"2021","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/33579706","citation_count":35,"is_preprint":false},{"pmid":"23874955","id":"PMC_23874955","title":"sox4 and sox11 function during Xenopus laevis eye development.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23874955","citation_count":35,"is_preprint":false},{"pmid":"32909943","id":"PMC_32909943","title":"SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells.","date":"2020","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/32909943","citation_count":34,"is_preprint":false},{"pmid":"36882421","id":"PMC_36882421","title":"SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/36882421","citation_count":33,"is_preprint":false},{"pmid":"30530749","id":"PMC_30530749","title":"Regulation of SOX11 expression through CCND1 and STAT3 in mantle cell lymphoma.","date":"2018","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/30530749","citation_count":31,"is_preprint":false},{"pmid":"30922366","id":"PMC_30922366","title":"Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8.","date":"2019","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/30922366","citation_count":31,"is_preprint":false},{"pmid":"24589730","id":"PMC_24589730","title":"Sox11 promotes endogenous neurogenesis and locomotor recovery in mice spinal cord injury.","date":"2014","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/24589730","citation_count":28,"is_preprint":false},{"pmid":"35341651","id":"PMC_35341651","title":"SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile.","date":"2022","source":"Genetics in medicine : official journal of the American College of Medical Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35341651","citation_count":28,"is_preprint":false},{"pmid":"25773392","id":"PMC_25773392","title":"The role of tumor suppressor gene SOX11 in prostate cancer.","date":"2015","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25773392","citation_count":28,"is_preprint":false},{"pmid":"33441400","id":"PMC_33441400","title":"Posttranslational Modification of Sox11 Regulates RGC Survival and Axon Regeneration.","date":"2021","source":"eNeuro","url":"https://pubmed.ncbi.nlm.nih.gov/33441400","citation_count":27,"is_preprint":false},{"pmid":"30619460","id":"PMC_30619460","title":"Different Effect of Sox11 in Retinal Ganglion Cells Survival and Axon Regeneration.","date":"2018","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30619460","citation_count":27,"is_preprint":false},{"pmid":"22331573","id":"PMC_22331573","title":"Sox11 modulates brain-derived neurotrophic factor expression in an exon promoter-specific manner.","date":"2012","source":"Journal of neuroscience research","url":"https://pubmed.ncbi.nlm.nih.gov/22331573","citation_count":27,"is_preprint":false},{"pmid":"30517979","id":"PMC_30517979","title":"SOX11 regulates apoptosis and cell cycle in hepatocellular carcinoma via Wnt/β-catenin signaling pathway.","date":"2018","source":"Biotechnology and applied biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30517979","citation_count":26,"is_preprint":false},{"pmid":"23466598","id":"PMC_23466598","title":"SOXC transcription factors in mantle cell lymphoma: the role of promoter methylation in SOX11 expression.","date":"2013","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/23466598","citation_count":26,"is_preprint":false},{"pmid":"20919851","id":"PMC_20919851","title":"SOX11 expression in mantle cell lymphoma.","date":"2010","source":"Leukemia & lymphoma","url":"https://pubmed.ncbi.nlm.nih.gov/20919851","citation_count":25,"is_preprint":false},{"pmid":"32043610","id":"PMC_32043610","title":"Upregulation of SOX11 enhances tamoxifen resistance and promotes epithelial-to-mesenchymal transition via slug in MCF-7 breast cancer cells.","date":"2020","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/32043610","citation_count":25,"is_preprint":false},{"pmid":"22465478","id":"PMC_22465478","title":"WT1 and Sox11 regulate synergistically the promoter of the Wnt4 gene that encodes a critical signal for nephrogenesis.","date":"2012","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/22465478","citation_count":25,"is_preprint":false},{"pmid":"24402778","id":"PMC_24402778","title":"Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity.","date":"2013","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/24402778","citation_count":25,"is_preprint":false},{"pmid":"31173278","id":"PMC_31173278","title":"MicroRNA-204-5p targets SOX11 to regulate the inflammatory response in spinal cord injury.","date":"2019","source":"European review for medical and pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/31173278","citation_count":25,"is_preprint":false},{"pmid":"29158064","id":"PMC_29158064","title":"miR-223 is repressed and correlates with inferior clinical features in mantle cell lymphoma through targeting SOX11.","date":"2017","source":"Experimental hematology","url":"https://pubmed.ncbi.nlm.nih.gov/29158064","citation_count":24,"is_preprint":false},{"pmid":"28466437","id":"PMC_28466437","title":"Role of SOX11 and Genetic Events Cooperating with Cyclin D1 in Mantle Cell Lymphoma.","date":"2017","source":"Current oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/28466437","citation_count":23,"is_preprint":false},{"pmid":"29459093","id":"PMC_29459093","title":"Sox11 gene disruption causes congenital anomalies of the kidney and urinary tract (CAKUT).","date":"2018","source":"Kidney international","url":"https://pubmed.ncbi.nlm.nih.gov/29459093","citation_count":22,"is_preprint":false},{"pmid":"22738398","id":"PMC_22738398","title":"Expanded clinical and experimental use of SOX11 - using a monoclonal antibody.","date":"2012","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/22738398","citation_count":22,"is_preprint":false},{"pmid":"29209164","id":"PMC_29209164","title":"Differential Expression of Sox11 and Bdnf mRNA Isoforms in the Injured and Regenerating Nervous Systems.","date":"2017","source":"Frontiers in molecular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/29209164","citation_count":21,"is_preprint":false},{"pmid":"23313252","id":"PMC_23313252","title":"Expression of Sox4 and Sox11 is regulated by multiple mechanisms during retinal development.","date":"2013","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/23313252","citation_count":21,"is_preprint":false},{"pmid":"32045135","id":"PMC_32045135","title":"LINC00961 inhibits the migration and invasion of colon cancer cells by sponging miR-223-3p and targeting SOX11.","date":"2020","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/32045135","citation_count":21,"is_preprint":false},{"pmid":"30026822","id":"PMC_30026822","title":"Aberrant methylation of FAT4 and SOX11 in peripheral blood leukocytes and their association with gastric cancer risk.","date":"2018","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/30026822","citation_count":21,"is_preprint":false},{"pmid":"26826126","id":"PMC_26826126","title":"Ablation of the Sox11 Gene Results in Clefting of the Secondary Palate Resembling the Pierre Robin Sequence.","date":"2016","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26826126","citation_count":21,"is_preprint":false},{"pmid":"29437512","id":"PMC_29437512","title":"Observation of Cleft Palate in an Individual with SOX11 Mutation: Indication of a Role for SOX11 in Human Palatogenesis.","date":"2017","source":"The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association","url":"https://pubmed.ncbi.nlm.nih.gov/29437512","citation_count":20,"is_preprint":false},{"pmid":"26949534","id":"PMC_26949534","title":"SOX11 is a biomarker for cyclin D1-negative mantle cell lymphoma.","date":"2016","source":"Biomarker research","url":"https://pubmed.ncbi.nlm.nih.gov/26949534","citation_count":20,"is_preprint":false},{"pmid":"24001358","id":"PMC_24001358","title":"The role of SOX11 in mantle cell lymphoma.","date":"2013","source":"Leukemia research","url":"https://pubmed.ncbi.nlm.nih.gov/24001358","citation_count":20,"is_preprint":false},{"pmid":"29973868","id":"PMC_29973868","title":"Phosphorylation Modulates the Subcellular Localization of SOX11.","date":"2018","source":"Frontiers in molecular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/29973868","citation_count":20,"is_preprint":false},{"pmid":"23619925","id":"PMC_23619925","title":"Sox11 expression in astrocytic gliomas: correlation with nestin/c-Met/IDH1-R132H expression phenotypes, p-Stat-3 and survival.","date":"2013","source":"British journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/23619925","citation_count":20,"is_preprint":false},{"pmid":"30935961","id":"PMC_30935961","title":"SOX11 hypermethylation as a tumor biomarker in endometrial cancer.","date":"2019","source":"Biochimie","url":"https://pubmed.ncbi.nlm.nih.gov/30935961","citation_count":19,"is_preprint":false},{"pmid":"28915052","id":"PMC_28915052","title":"Mass Spectrometric Analysis of SOX11-Binding Proteins in Head and Neck Cancer Cells Demonstrates the Interaction of SOX11 and HSP90α.","date":"2017","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/28915052","citation_count":19,"is_preprint":false},{"pmid":"35368699","id":"PMC_35368699","title":"miR-145-5p Inhibits Neuroendocrine Differentiation and Tumor Growth by Regulating the SOX11/MYCN Axis in Prostate cancer.","date":"2022","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35368699","citation_count":19,"is_preprint":false},{"pmid":"31035284","id":"PMC_31035284","title":"A novel human stem cell model for Coffin-Siris syndrome-like syndrome reveals the importance of SOX11 dosage for neuronal differentiation and survival.","date":"2019","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31035284","citation_count":19,"is_preprint":false},{"pmid":"31173643","id":"PMC_31173643","title":"Increased tumour angiogenesis in SOX11-positive mantle cell lymphoma.","date":"2019","source":"Histopathology","url":"https://pubmed.ncbi.nlm.nih.gov/31173643","citation_count":18,"is_preprint":false},{"pmid":"31296581","id":"PMC_31296581","title":"Highly sensitive and specific in situ hybridization assay for quantification of SOX11 mRNA in mantle cell lymphoma reveals association of TP53 mutations with negative and low SOX11 expression.","date":"2019","source":"Haematologica","url":"https://pubmed.ncbi.nlm.nih.gov/31296581","citation_count":18,"is_preprint":false},{"pmid":"21479697","id":"PMC_21479697","title":"The expression of SOX11, cyclin D1, cyclin D2, and cyclin D3 in B-cell lymphocytic proliferative diseases.","date":"2011","source":"Medical oncology (Northwood, London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/21479697","citation_count":18,"is_preprint":false},{"pmid":"22827557","id":"PMC_22827557","title":"A highly sensitive and specific qPCR assay for quantification of the biomarker SOX11 in mantle cell lymphoma.","date":"2012","source":"European journal of haematology","url":"https://pubmed.ncbi.nlm.nih.gov/22827557","citation_count":17,"is_preprint":false},{"pmid":"30221780","id":"PMC_30221780","title":"SOX11: a potentially useful marker in surgical pathology: a systematic analysis of SOX11 expression in epithelial and non-epithelial tumours.","date":"2018","source":"Histopathology","url":"https://pubmed.ncbi.nlm.nih.gov/30221780","citation_count":17,"is_preprint":false},{"pmid":"18261853","id":"PMC_18261853","title":"Expression of Sox11 and Brn transcription factors during development and following transient forebrain ischemia in the rat.","date":"2008","source":"Neuroscience letters","url":"https://pubmed.ncbi.nlm.nih.gov/18261853","citation_count":17,"is_preprint":false},{"pmid":"30720133","id":"PMC_30720133","title":"Promoter hypermethylation of SOX11 promotes the progression of cervical cancer in vitro and in vivo.","date":"2019","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/30720133","citation_count":17,"is_preprint":false},{"pmid":"38620074","id":"PMC_38620074","title":"SOX11 expression is restricted to EBV-negative Burkitt lymphoma and is associated with molecular genetic features.","date":"2024","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/38620074","citation_count":16,"is_preprint":false},{"pmid":"31078342","id":"PMC_31078342","title":"SOX11 promotes osteoarthritis through induction of TNF-α.","date":"2019","source":"Pathology, research and practice","url":"https://pubmed.ncbi.nlm.nih.gov/31078342","citation_count":16,"is_preprint":false},{"pmid":"25880212","id":"PMC_25880212","title":"DNA methylation and histone modifications regulate SOX11 expression in lymphoid and solid cancer cells.","date":"2015","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/25880212","citation_count":16,"is_preprint":false},{"pmid":"38084140","id":"PMC_38084140","title":"Inhibition of hepatocellular carcinoma growth via modulation of the miR-221/SOX11 axis by curcumin and berberine.","date":"2023","source":"PeerJ","url":"https://pubmed.ncbi.nlm.nih.gov/38084140","citation_count":16,"is_preprint":false},{"pmid":"25229384","id":"PMC_25229384","title":"Utility and diagnostic pitfalls of SOX11 monoclonal antibodies in mantle cell lymphoma and other lymphoproliferative disorders.","date":"2014","source":"Applied immunohistochemistry & molecular morphology : AIMM","url":"https://pubmed.ncbi.nlm.nih.gov/25229384","citation_count":16,"is_preprint":false},{"pmid":"35305240","id":"PMC_35305240","title":"SOX11-dependent CATSPER1 expression controls colon cancer cell growth through regulation the PI3K/AKT signaling pathway.","date":"2022","source":"Genes & genomics","url":"https://pubmed.ncbi.nlm.nih.gov/35305240","citation_count":15,"is_preprint":false},{"pmid":"29746989","id":"PMC_29746989","title":"Increased Expression of Transcription Factor SRY-box-Containing Gene 11 (Sox11) Enhances Neurite Growth by Regulating Neurotrophic Factor Responsiveness.","date":"2018","source":"Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/29746989","citation_count":15,"is_preprint":false},{"pmid":"26757780","id":"PMC_26757780","title":"SOX11 and HIG-2 are cross-regulated and affect growth in mantle cell lymphoma.","date":"2016","source":"Leukemia & lymphoma","url":"https://pubmed.ncbi.nlm.nih.gov/26757780","citation_count":14,"is_preprint":false},{"pmid":"33801642","id":"PMC_33801642","title":"SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant Melanoma.","date":"2021","source":"Life (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/33801642","citation_count":14,"is_preprint":false},{"pmid":"34442467","id":"PMC_34442467","title":"Multi-Omics Analysis of SOX4, SOX11, and SOX12 Expression and the Associated Pathways in Human Cancers.","date":"2021","source":"Journal of personalized medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34442467","citation_count":13,"is_preprint":false},{"pmid":"35317520","id":"PMC_35317520","title":"LINC01296 promotes neuroblastoma tumorigenesis via the NCL-SOX11 regulatory complex.","date":"2022","source":"Molecular therapy oncolytics","url":"https://pubmed.ncbi.nlm.nih.gov/35317520","citation_count":13,"is_preprint":false},{"pmid":"30617615","id":"PMC_30617615","title":"Sox11-modified mesenchymal stem cells accelerate cartilage defect repair in SD rats.","date":"2019","source":"Cell and tissue research","url":"https://pubmed.ncbi.nlm.nih.gov/30617615","citation_count":13,"is_preprint":false},{"pmid":"33177836","id":"PMC_33177836","title":"LncRNA RNF144A-AS1 Promotes Bladder Cancer Progression via RNF144A-AS1/miR-455-5p/SOX11 Axis.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/33177836","citation_count":13,"is_preprint":false},{"pmid":"36551589","id":"PMC_36551589","title":"Systematic Investigation of the Multifaceted Role of SOX11 in Cancer.","date":"2022","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/36551589","citation_count":12,"is_preprint":false},{"pmid":"39135278","id":"PMC_39135278","title":"microRNA-125b-5p alleviated CCI-induced neuropathic pain and modulated neuroinflammation via targeting SOX11.","date":"2024","source":"Synapse (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/39135278","citation_count":12,"is_preprint":false},{"pmid":"33629302","id":"PMC_33629302","title":"LINC01605 regulates proliferation, migration and invasion of colorectal cancer cells via targeting miR-3960/SOX11.","date":"2021","source":"European review for medical and pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33629302","citation_count":12,"is_preprint":false},{"pmid":"25234735","id":"PMC_25234735","title":"Study of promoter DNA methylation of Sox11 and its correlation with tissue-specific expression in the laboratory mouse.","date":"2014","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/25234735","citation_count":11,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":49926,"output_tokens":9352,"usd":0.145029,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":19733,"output_tokens":4236,"usd":0.102282,"stage2_stop_reason":"end_turn"},"total_usd":0.247311,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2008,\n      \"finding\": \"The C-terminal 33 residues of SOX11 constitute its transactivation domain (TAD). SOX11 activates transcription more efficiently than SOX4 and SOX12, owing to a more stable alpha-helical structure of its TAD. Acidic domains and the TAD itself interfere with DNA binding.\",\n      \"method\": \"Reporter gene transactivation assays, domain mapping, structural analysis of TAD\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reporter assays with domain mutagenesis, multiple orthogonal approaches (reporter gene assays + structural analysis), single lab\",\n      \"pmids\": [\"18403418\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Cryo-EM structures show that SOX11 HMG domain binds nucleosomal DNA at superhelical location 2, locally distorting DNA and facilitating detachment of terminal nucleosomal DNA from the histone octamer, thereby increasing DNA accessibility. SOX11 binding also repositions the N-terminal tail of histone H4 including K16.\",\n      \"method\": \"Cryo-electron microscopy structure determination\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structural determination at high resolution with functional validation, published in Nature\",\n      \"pmids\": [\"32350470\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"SOX11 is required for neuron survival and neurite outgrowth. siRNA-mediated knockdown in Neuro2a cells increased apoptosis and decreased neurite growth, upregulated pro-apoptotic BNIP3, and decreased anti-apoptotic TANK. In primary DRG neurons, SOX11 knockdown decreased neurite growth/branching and reduced Arpc3 (actin organizing protein) mRNA.\",\n      \"method\": \"RNAi knockdown in Neuro2a cells and primary DRG neurons, gene expression analysis\",\n      \"journal\": \"Neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined cellular phenotype and target gene identification, single lab, two cell models\",\n      \"pmids\": [\"17055661\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"In vivo siRNA-mediated knockdown of Sox11 in injured mouse saphenous nerve transiently inhibited peripheral nerve regeneration of both myelinated and unmyelinated axons. Sox11 knockdown reduced ATF3 expression at transcriptional and translational levels in injured neurons.\",\n      \"method\": \"In vivo siRNA injection via Penetratin conjugation, electron microscopy, immunostaining\",\n      \"journal\": \"Brain research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo loss-of-function with morphological and molecular readouts, single lab, two orthogonal methods\",\n      \"pmids\": [\"19133245\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"SOX11 promotes tumor growth in MCL xenograft models. By ChIP-microarray combined with gene expression profiling upon SOX11 knockdown, SOX11 directly targets PAX5. SOX11 silencing downregulates PAX5, induces BLIMP1, and promotes plasmacytic differentiation, blocking terminal B-cell differentiation.\",\n      \"method\": \"ChIP-microarray, gene expression profiling, siRNA knockdown, xenograft mouse model\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — ChIP-microarray identifies direct targets, knockdown with phenotypic rescue, xenograft model, multiple orthogonal methods\",\n      \"pmids\": [\"23321250\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"SOX11 directly binds regulatory regions of CXCR4 and PTK2 (FAK), upregulating their expression in MCL cells. This activates PI3K/AKT and ERK1/2 FAK-downstream pathways, enhancing cell migration, stromal adhesion, endothelial transmigration, proliferation, and cell adhesion-mediated drug resistance.\",\n      \"method\": \"ChIP, gene expression analysis, siRNA knockdown, functional migration/adhesion assays, xenograft models, FAK/CXCR4 inhibitor treatment\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — ChIP demonstrates direct binding, multiple functional assays, in vivo xenograft validation, single lab\",\n      \"pmids\": [\"28533307\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"SOX11 directly transcriptionally upregulates PDGFA in MCL cells. SOX11-positive MCL tumors had higher microvascular density and angiogenic gene signatures; conditioned media from SOX11+ cells promoted endothelial cell proliferation, migration, and tube formation. PDGFA inhibition impaired SOX11-enhanced angiogenesis.\",\n      \"method\": \"ChIP, gene expression profiling, conditioned media assays, endothelial cell functional assays, xenograft models with imatinib treatment\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — ChIP demonstrates direct SOX11-PDGFA regulation, multiple orthogonal functional assays, in vivo validation\",\n      \"pmids\": [\"25092176\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"SOX11 directly reduces tumor growth in hematopoietic malignancies. siRNA knockdown and ectopic overexpression alter proliferation. Gene expression analysis identified Rb-E2F cell cycle regulatory pathways as associated with SOX11-induced growth reduction. SOX11 is epigenetically silenced by DNA methylation in B-cell lymphomas.\",\n      \"method\": \"siRNA knockdown, ectopic overexpression, GeneChip expression analysis, promoter methylation analysis\",\n      \"journal\": \"Molecular cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — both loss- and gain-of-function with pathway identification, single lab, multiple orthogonal approaches\",\n      \"pmids\": [\"20624318\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"SOX11 epigenetic activation in aggressive B-cell lymphomas is mediated by a shift from inactivating histone marks (H3K9me2, H3K27me3) to activating histone marks (H3K9/14Ac, H3K4me3). SOX11 silencing in non-expressing lymphoid cells correlates with H3K27me3. HDAC inhibitor SAHA reversed SOX11 silencing but DNA methyltransferase inhibitor AZA did not.\",\n      \"method\": \"ChIP, bisulfite sequencing, HDAC inhibitor and DNA methyltransferase inhibitor treatment\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP for histone marks, pharmacological intervention, single lab, multiple cell types examined\",\n      \"pmids\": [\"21738649\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Sox11 knockout mice show severe reduction in sensory neuron survival in trigeminal and dorsal root ganglia, and arrest of axonal outgrowth in vivo and in vitro. This axonal growth defect could not be fully rescued by blocking cell death, indicating a cell-death-independent role in axon growth.\",\n      \"method\": \"Sox11 knockout mouse (knockin of LacZ replacing Sox11 coding region), histological analysis, in vitro axon growth assay\",\n      \"journal\": \"Developmental dynamics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic knockout model with defined cellular phenotype, rescue experiments, two orthogonal readouts\",\n      \"pmids\": [\"21117150\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"In sympathetic nervous system development, Sox11 is required early for proliferation of tyrosine hydroxylase-expressing cells, while Sox4 ensures their survival at later stages. In double Sox4/Sox11 knockout mice, sympathetic ganglia remain hypoplastic due to consecutive proliferation and survival defects, leading to dysautonomia.\",\n      \"method\": \"Mouse mutagenesis (conditional knockouts), overexpression in chicken, histological analysis\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic mouse mutagenesis with epistasis, two species, defined cellular phenotype\",\n      \"pmids\": [\"20147379\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Sox11 is required for both embryonic and adult neurogenesis. Sox11 null embryos develop small, disorganized brains with transient NPC proliferation deficits. Conditional Sox11 deletion in adult NPCs blunts proliferation in the SGZ. Functional genomics identified potential downstream target genes.\",\n      \"method\": \"Sox11 conditional knockout mice (Cre-loxP), BrdU labeling, functional genomics/transcriptomics\",\n      \"journal\": \"Developmental dynamics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic knockout with defined proliferation phenotype, multiple developmental stages examined, downstream target identification\",\n      \"pmids\": [\"23483698\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Phosphorylation of SOX11 at serine 30 promotes nuclear over cytoplasmic localization. Mass spectrometry identified 10 putative phosphorylated serine residues in SOX11. Western blot of embryonic mouse brain lysates confirmed SOX11 is post-translationally modified by phosphorylation.\",\n      \"method\": \"Mass spectrometry, phospho-mutant analysis, Western blot, subcellular localization assays\",\n      \"journal\": \"Frontiers in molecular neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mass spectrometry identification plus mutagenesis of specific residue with localization readout, single lab\",\n      \"pmids\": [\"29973868\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"USP11 deubiquitinase stabilizes SOX11 protein in the developing cortex. USP11 deficiency impairs layer 6 neuron production and delays neuronal migration. Disease-associated USP11 mutant fails to stabilize SOX11. USP11 ablation reduces SOX11 protein despite induction of Sox11 mRNA, indicating post-translational regulation.\",\n      \"method\": \"Mouse Usp11 knockout, cortical analysis, co-immunoprecipitation, neuronal migration assays\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic knockout plus substrate identification via Co-IP, disease-mutant validation, multiple phenotypic readouts, single lab\",\n      \"pmids\": [\"33579706\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SUMOylation of SOX11 at lysine 91 (K91) regulates its nuclear localization and function. Non-SUMOylatable SOX11-K91A shows increased nuclear localization and enhanced RGC differentiation in vitro, but promotes RGC death and stronger axon regeneration after optic nerve injury in vivo. RNA-seq showed Sox11 and Sox11K91A increase axon growth gene expression but downregulate Spp1 and Opn4.\",\n      \"method\": \"Site-directed mutagenesis (K91A), in vitro RGC differentiation assay, optic nerve crush model in vivo, RNA-seq\",\n      \"journal\": \"eNeuro\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — mutagenesis of specific PTM site with subcellular localization and functional consequences both in vitro and in vivo, transcriptomic analysis\",\n      \"pmids\": [\"33441400\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Sox11 modulates BDNF transcription in an exon promoter-specific manner. Sox11 activates BDNF exon I and IV promoters via Sox binding motif 5'-AACAAAG-3'; mutation of these sites reduces activation. Sox11 overexpression in Neuro2a cells elevated exon IV and VII BDNF transcripts.\",\n      \"method\": \"Luciferase reporter assays, Sox binding site mutagenesis, RT-PCR expression analysis\",\n      \"journal\": \"Journal of neuroscience research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — reporter assay with mutagenesis validation, single lab, focused on transcriptional mechanism\",\n      \"pmids\": [\"22331573\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"SOX11 and WT1 synergistically regulate the Wnt4 promoter in embryonic kidney mesenchyme. Sox11 and WT1 co-immunoprecipitate from embryonic kidney cells. Dominant negative WT1 mutants (P129L, F154S) that cannot interact with Sox11 cannot activate Wnt4. Morpholino knockdown of wt1 or sox11 in Xenopus inhibited Wnt4 expression in the pronephros.\",\n      \"method\": \"Co-immunoprecipitation, luciferase reporter assay, dominant-negative mutants, morpholino knockdown in Xenopus\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — Co-IP demonstrates protein complex, reporter assays with dominant negatives, in vivo morpholino validation, multiple orthogonal methods\",\n      \"pmids\": [\"22465478\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"SOX11 directly binds conserved SOX family binding sites in the 5' UTR of GDF5 and activates GDF5 expression. SOX11 overexpression in chick limb micromass cultures directly activates GDF5, and enhances Gdf5 expression in developing chick limbs.\",\n      \"method\": \"In vitro reporter assay, micromass cultures, RCAS virus-mediated overexpression in chick limb, binding site analysis\",\n      \"journal\": \"BMC developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — direct binding to promoter demonstrated, multiple model systems, single lab\",\n      \"pmids\": [\"23356643\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SOX11 expression in MCL is regulated by CCND1 and STAT3. CCND1 increases SOX11 transcription by sequestering HDAC1 and HDAC2 from the SOX11 locus, leading to increased H3K9/14 acetylation. STAT3 activation decreases SOX11 expression; JAK1/JAK2 inhibition or STAT3 knockdown increases SOX11 expression.\",\n      \"method\": \"ChIP, Co-IP, RNAi knockdown, ectopic overexpression, HDAC inhibitor treatment, cytokine stimulation assays\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — ChIP demonstrates HDAC displacement from SOX11 locus, Co-IP shows CCND1-HDAC interaction, multiple orthogonal mechanistic approaches, single lab\",\n      \"pmids\": [\"30530749\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SOX11 overexpression in B cells drives BCR signaling hyperactivation (pBTK and downstream molecules) and produces an oligoclonal B-cell hyperplasia with MCL-like immunophenotype (CD5+CD19+CD23-). Serial bone marrow transplant from transgenic donors produces lethal disease with decreasing latency.\",\n      \"method\": \"Transgenic mouse model (Eμ-SOX11-EGFP), phosphocytometric mass cytometry (CyTOF), bone marrow transplantation\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — transgenic mouse model with defined signaling phenotype, transplantation experiments confirming tumorigenicity, single lab\",\n      \"pmids\": [\"29615403\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Sox11 suppresses dendritic morphogenesis of excitatory neurons in mouse cerebral cortex. Loss-of-function causes precocious neurite branching and a neuronal migration defect; gain-of-function inhibits dendritic morphogenesis. Arrival at final cortical position induces Sox11 downregulation, which is required to permit dendritic branching.\",\n      \"method\": \"In utero electroporation and postnatal electroporation (loss- and gain-of-function), morphological analysis\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — both loss- and gain-of-function with defined cellular phenotype, single lab, in vivo model\",\n      \"pmids\": [\"27225767\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SOX11 and SOX4 regulate embryonic epidermal state and are required for wound re-epithelialization. They regulate cytoskeletal/ECM genes and directly target FSCN1 (fascin), which mediates cell migration. Sox11/Sox4 deficiency accelerates differentiation and dramatically impairs cell motility.\",\n      \"method\": \"Mouse knockout models, chromatin immunoprecipitation, gene expression profiling, wound healing assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — genetic knockouts, ChIP demonstrating direct target, multiple functional readouts, single lab\",\n      \"pmids\": [\"31492871\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Sox11 overexpression in MSCs transcriptionally activates Runx2 and CXCR4 expression (demonstrated by dual-luciferase reporter assay) and activates the BMP/Smad signaling pathway, enhancing trilineage differentiation and migration of MSCs.\",\n      \"method\": \"Lentiviral overexpression, dual-luciferase reporter assay, ectopic bone formation, western blot, open fracture rat model\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — reporter assay for direct transcriptional targets, multiple differentiation assays, in vivo model, single lab\",\n      \"pmids\": [\"25466891\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Wnt7b induces Sox11 expression in BMSCs via a β-catenin-independent, Ca2+-dependent Nfatc1 signaling pathway. ChIP-qPCR showed Nfatc1 directly binds the Sox11 promoter. Sox11 in turn transcriptionally activates Ccnb1, Sox2 (proliferation) and Runx2, Sp7 (osteogenesis).\",\n      \"method\": \"ChIP-qPCR, RNA-seq, shRNA knockdown, transgenic mice, immunofluorescence, ex vivo transplantation\",\n      \"journal\": \"Stem cells (Dayton, Ohio)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — ChIP demonstrates Nfatc1-Sox11 promoter binding, multiple downstream targets identified, single lab\",\n      \"pmids\": [\"32346881\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SOX11 directly upregulates CD70 expression in MCL cells. CD70 overexpression in SOX11+ MCL is associated with increased Treg cell infiltration and an immunosuppressive tumor microenvironment. CD40L stimulation induces CD70 in SOX11+ but not SOX11- MCL cells in vitro.\",\n      \"method\": \"ChIP (binding to CD70 regulatory regions), gene expression analysis, immunohistochemistry, in vitro stimulation assays\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP demonstrates direct SOX11-CD70 regulation, multiple validation approaches, single lab\",\n      \"pmids\": [\"34189576\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Sox11 overexpression in glioma-initiating cells (NSC-derived) prevents tumorigenesis by inducing neuronal differentiation, accompanied by decreased plagl1 expression. Plagl1 overexpression abolishes neuronal commitment and induces tumorigenicity. Sox11 loss is found in human glioma-initiating cells, and Sox11 overexpression prevents their tumorigenesis in vivo.\",\n      \"method\": \"Gene expression profiling, overexpression assays, in vivo tumorigenesis, limiting dilution assays\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain-of-function with in vivo tumorigenesis readout, epistasis with plagl1, single lab\",\n      \"pmids\": [\"19808959\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Endogenous SOX11 directly binds the SDCCAG8 gene promoter in highly invasive HNSCC cells. Wild-type SOX11 but not a DNA-binding mutant activates SDCCAG8 promoter activity. Inhibitory effects of SOX11 knockdown on proliferation, migration, and invasion were partially rescued by SDCCAG8 overexpression.\",\n      \"method\": \"ChIP, luciferase reporter assay, mutagenesis, quantitative proteomics, rescue assay\",\n      \"journal\": \"Journal of experimental & clinical cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — ChIP and reporter assay with mutagenesis demonstrate direct target regulation, rescue assay validates pathway, single lab\",\n      \"pmids\": [\"30922366\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"SOX11 binds the slug (SNAI2) promoter and activates its transcription in MCF-7 tamoxifen-resistant breast cancer cells, promoting epithelial-to-mesenchymal transition and suppressing ESR1 expression.\",\n      \"method\": \"Chromatin immunoprecipitation, luciferase reporter assay, gene expression analysis\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Weak — ChIP and reporter assay demonstrate direct transcriptional regulation, single lab, single model\",\n      \"pmids\": [\"32043610\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SOX11 is a core regulatory circuitry (CRC) transcription factor in adrenergic neuroblastoma. SOX11 directly regulates 10 SWI/SNF core components (including SMARCC1, SMARCA4/BRG1, ARID1A), HDAC2, PRC1 component CBX2, KDM1A/LSD1, and c-MYB. SOX11 is regulated by multiple adrenergic-specific super-enhancers.\",\n      \"method\": \"ChIP-seq, enhancer analysis, gene expression dependency analysis, neuroblastoma cell line functional studies\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — ChIP-seq demonstrates direct binding and regulation of chromatin regulatory complex components, super-enhancer analysis, multiple orthogonal approaches\",\n      \"pmids\": [\"36882421\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"SOX11 binds to HSP90α (HSP90AA1) in head and neck cancer cells. The interaction was identified by Co-IP/LC-MS/MS and validated by Co-IP with western blotting.\",\n      \"method\": \"Co-immunoprecipitation, liquid chromatography-tandem mass spectrometry (LC-MS/MS), western blotting\",\n      \"journal\": \"Journal of proteome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — Co-IP/MS identification validated by reciprocal Co-IP, single lab, functional consequence of interaction not directly established\",\n      \"pmids\": [\"28915052\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SOX11 overexpression in HCC cells enhances nemo-like kinase expression and TCF4 phosphorylation, thereby inhibiting Wnt/β-catenin signaling and promoting growth inhibition and apoptosis.\",\n      \"method\": \"Overexpression assays, western blot, cell viability and apoptosis assays\",\n      \"journal\": \"Biotechnology and applied biochemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single overexpression system, signaling pathway changes by western blot, single lab, limited mechanistic depth\",\n      \"pmids\": [\"30517979\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Cell-type-specific deletion shows Sox11 is required for proper outflow tract development in both mesodermal cells and neural crest cells. Sox4 and Sox11 become essential after neural crest arrival in the outflow tract for differentiation and interaction through regulation of cytoskeletal, cell adhesion, and ECM molecules.\",\n      \"method\": \"Cell-type-specific conditional deletion in mouse (mesoderm and neural crest), phenotypic analysis\",\n      \"journal\": \"Cellular and molecular life sciences\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with cell-type-specific deletion, defined phenotypic readouts, molecular pathway identification\",\n      \"pmids\": [\"24310815\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Sox11 disruption in mice causes CAKUT including duplex kidney formation. SOX11 directly binds and regulates a locus control region of the protocadherin B cluster. SOX11 regulates elongation of Henle's loop. A CAKUT-associated SOX11 variant identified in patients interferes with SOX11 transactivation capacity.\",\n      \"method\": \"Sox11 knockout mouse, ChIP demonstrating direct binding to protocadherin B locus control region, transactivation assays\",\n      \"journal\": \"Kidney international\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — genetic knockout with defined developmental phenotype, ChIP demonstrates direct binding, human variant functional analysis, single lab\",\n      \"pmids\": [\"29459093\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Sox11 deficiency causes cleft palate through mandibular hypoplasia; Sox11 loss reduces cell proliferation in mandibular mesenchyme via Cyclin D1. In vitro assays show Sox11 directly regulates Fgf9 expression, and FGF9 protein application to Sox11-deficient palatal shelves restores BrdU incorporation.\",\n      \"method\": \"Sox11 knockout mouse, BrdU proliferation assay, gene expression analysis, in vitro FGF9 rescue assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic knockout with phenotypic analysis, direct target (Fgf9) validated by rescue assay, single lab\",\n      \"pmids\": [\"26826126\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SOX11 promotes cell migration in wounded skin by activating expression of FSCN1 (fascin actin-bundling protein 1) as a direct transcriptional target. Sox11/Sox4 deficiency impairs cell motility and re-epithelialization.\",\n      \"method\": \"ChIP, mouse knockout models, wound healing assays, gene expression profiling\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — ChIP demonstrates direct SOX11-FSCN1 regulation, genetic knockouts with functional phenotype, single lab\",\n      \"pmids\": [\"31492871\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"LHX2 binds distal regulatory elements of Sox11 in cortical progenitors and interacts with NuRD complex subunits LSD1, HDAC2, and RBBP4 to maintain repressive chromatin at the Sox11 locus. Loss of LHX2 increases active histone marks at Sox11 loci and increases Sox11 expression, while LHX2 overexpression decreases it.\",\n      \"method\": \"ChIP, Co-IP (LHX2 with NuRD complex components), conditional knockout, overexpression, histone mark analysis\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP demonstrates direct binding, Co-IP shows protein complex, genetic manipulation with molecular readout, single lab\",\n      \"pmids\": [\"28053041\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"LINC01296 binds nucleolin (NCL) and forms a complex that activates SOX11 gene transcription, promoting neuroblastoma tumorigenesis. Silencing LINC01296 reduces SOX11 expression; RNA pull-down validated the LINC01296-NCL interaction.\",\n      \"method\": \"RNA pull-down assay, Co-IP, luciferase reporter assay, siRNA knockdown, in vivo xenograft\",\n      \"journal\": \"Molecular therapy oncolytics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNA pull-down validates lncRNA-protein interaction, downstream SOX11 transcriptional activation demonstrated, in vivo validation, single lab\",\n      \"pmids\": [\"35317520\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Sox11 in spinal cord injury promotes neuronal differentiation of endogenous neural stem cells and induces BDNF expression in the injured cord, improving locomotor recovery.\",\n      \"method\": \"Lentiviral Sox11 delivery to injured mouse spinal cord, immunostaining, behavioral assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — gain-of-function in vivo with cellular and behavioral readouts, molecular mechanism not deeply probed, single lab\",\n      \"pmids\": [\"24589730\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SOX11 confers a hybrid epithelial/mesenchymal (E/M) state in ER-negative breast cancer cells, leading to alterations in metastatic tropism (increased brain and bone metastasis, decreased lung metastasis) in xenograft models.\",\n      \"method\": \"SOX11 overexpression in DCIS.com cells, xenograft mouse model, single-cell analysis, E/M marker analysis\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain-of-function with defined in vivo metastatic phenotype, single lab, molecular characterization\",\n      \"pmids\": [\"32909943\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"SOX11 promoter in non-malignant cells shows low methylation with strong H3K27me3 enrichment. In cancer cells with low SOX11 methylation, HDAC inhibitors (vorinostat, trichostatin A) can reactivate SOX11 expression, while cells with dense methylation are resistant to re-expression.\",\n      \"method\": \"Bisulfite sequencing, ChIP-qPCR for H3K27me3, HDAC inhibitor treatment, methylation assays in 42 cell lines\",\n      \"journal\": \"BMC cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP and methylation analysis across multiple cell lines with pharmacological validation, single lab\",\n      \"pmids\": [\"25880212\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SOX11 transcriptionally activates β-catenin expression in MSCs (core promoter region -242 to -1414 identified). Sox11 also interacts with β-catenin protein (co-immunoprecipitation) suggesting post-transcriptional regulation in addition to transcriptional activation.\",\n      \"method\": \"Dual-luciferase reporter assay, co-immunoprecipitation, quantitative RT-PCR, in vivo cartilage defect model\",\n      \"journal\": \"Cell and tissue research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Weak — reporter assay defines promoter region, Co-IP shows protein interaction, single lab, single model system\",\n      \"pmids\": [\"30617615\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SOX11 is a SOXC-group HMG-box transcription factor that acts as a pioneer factor, binding nucleosomal DNA at superhelical location 2 to locally distort DNA and increase chromatin accessibility; its transactivation domain (C-terminal 33 residues with a stable alpha-helical structure) drives target gene expression, while its activity and subcellular localization are regulated by post-translational modifications including phosphorylation at S30 (promoting nuclear localization) and SUMOylation at K91 (restricting nuclear localization); upstream regulators include CCND1 (which sequesters HDAC1/2 from the SOX11 locus to increase histone acetylation), STAT3 (which represses SOX11), USP11 deubiquitinase (which stabilizes SOX11 protein), and Wnt7b/Nfatc1 signaling; in neural development SOX11 promotes neuron survival, axon growth, and maturation while suppressing premature dendritic branching; in lymphoma, SOX11 drives MCL pathogenesis by blocking terminal B-cell differentiation through direct transcriptional activation of PAX5, promoting tumor angiogenesis via PDGFA, and enhancing BCR signaling and microenvironment interactions through CXCR4 and FAK; in other contexts SOX11 directly regulates GDF5, Wnt4, FSCN1, BDNF, Runx2, CXCR4, CD70, SDCCAG8, and SWI/SNF complex components including SMARCA4/BRG1.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SOX11 is an HMG-box transcription factor that functions as a pioneer factor and master regulator across neural development, tissue morphogenesis, and oncogenesis [#1, #4]. Structurally, its HMG domain engages nucleosomal DNA at superhelical location 2 to locally distort DNA, detach terminal nucleosomal DNA from the histone octamer, and reposition the histone H4 N-terminal tail, thereby increasing chromatin accessibility, while a C-terminal transactivation domain with a stable alpha-helical structure drives target gene expression more efficiently than its SOXC paralogs [#1, #0]. Its activity and nuclear localization are tuned by post-translational modification: phosphorylation at S30 promotes nuclear localization, SUMOylation at K91 restricts nuclear localization and constrains axon-growth programs, and the deubiquitinase USP11 stabilizes SOX11 protein to support cortical neuron production [#12, #14, #13]. In neural development SOX11 is required for neuron survival, proliferation of neural progenitors, and axon growth in both embryonic and adult contexts, while its downregulation upon neuronal maturation is required to permit dendritic branching [#9, #11, #20]. SOX11 governs morphogenesis of multiple tissues through direct transcriptional targets, including FSCN1 in epidermal wound re-epithelialization, GDF5 in limb, Fgf9 in palate, and a protocadherin B locus control region in kidney; a CAKUT-associated SOX11 variant impairing transactivation links SOX11 to congenital kidney malformation in patients [#34, #17, #33, #32]. In mantle cell lymphoma SOX11 drives pathogenesis by blocking terminal B-cell differentiation through direct activation of PAX5, promoting angiogenesis via PDGFA, and enhancing BCR signaling, stromal interactions and immune evasion through CXCR4, PTK2/FAK, and CD70; its own expression is set epigenetically by a shift from repressive to activating histone marks and by CCND1-mediated displacement of HDAC1/2 from the SOX11 locus [#4, #6, #5, #24, #18, #8]. SOX11 also acts as a core regulatory circuitry factor in adrenergic neuroblastoma, directly regulating SWI/SNF, NuRD, and PRC1 chromatin-machinery components [#28].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established that SOX11 is functionally required in neurons, not merely expressed there, by showing its loss kills neurons and stunts neurite growth.\",\n      \"evidence\": \"RNAi knockdown in Neuro2a and primary DRG neurons with apoptosis and neurite readouts\",\n      \"pmids\": [\"17055661\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct transcriptional targets driving survival vs. growth not separated\", \"Cell-autonomy in vivo not addressed\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Defined the structural basis of SOX11's transactivation by mapping the C-terminal TAD and explaining why SOX11 activates more strongly than its SOXC paralogs.\",\n      \"evidence\": \"Reporter transactivation assays, domain mapping, and TAD structural analysis\",\n      \"pmids\": [\"18403418\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Coactivators recruited by the TAD not identified\", \"Regulation of TAD/DNA-binding interference in cells unresolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Distinguished SOX11 from SOX4 functionally within the SOXC group, showing SOX11 drives early progenitor proliferation while SOX4 supports later survival.\",\n      \"evidence\": \"Conditional and double Sox4/Sox11 knockout mice plus chicken overexpression in sympathetic ganglia\",\n      \"pmids\": [\"20147379\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Target genes mediating proliferation vs. survival not defined\", \"Mechanism of paralog functional divergence unknown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Separated SOX11's survival and axon-growth functions genetically, proving a cell-death-independent role in axon outgrowth.\",\n      \"evidence\": \"Sox11 LacZ-knockin knockout mouse with histology and in vitro axon growth, including cell-death blockade\",\n      \"pmids\": [\"21117150\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct axon-growth target genes not identified\", \"How axon vs. survival programs are partitioned unclear\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Identified the central oncogenic mechanism in MCL: SOX11 directly activates PAX5 to enforce a B-cell program and block plasmacytic differentiation.\",\n      \"evidence\": \"ChIP-microarray, expression profiling, siRNA knockdown, and MCL xenografts\",\n      \"pmids\": [\"23321250\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full direct target network beyond PAX5 not mapped\", \"Cofactors at the PAX5 locus unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Explained how SOX11 reshapes the MCL microenvironment by directly activating PDGFA (angiogenesis) and CXCR4/PTK2-FAK (migration, adhesion, drug resistance).\",\n      \"evidence\": \"ChIP, functional migration/adhesion/angiogenesis assays, and xenografts with inhibitor treatment\",\n      \"pmids\": [\"25092176\", \"28533307\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative contribution of each target to tumor growth not quantified\", \"Direct vs. paracrine effects partly entangled\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Resolved how SOX11 expression is set in MCL, showing CCND1 displaces HDAC1/2 from the locus to raise histone acetylation while STAT3 represses it.\",\n      \"evidence\": \"ChIP, Co-IP, RNAi, overexpression, HDAC inhibitor and cytokine assays\",\n      \"pmids\": [\"30530749\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Transcription factors directing CCND1/HDAC to the locus unknown\", \"Interplay with DNA methylation status not fully integrated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Demonstrated SOX11 is a bona fide MCL driver in vivo, sufficient to hyperactivate BCR signaling and produce MCL-like disease.\",\n      \"evidence\": \"Eu-SOX11 transgenic mouse, CyTOF signaling analysis, serial bone marrow transplantation\",\n      \"pmids\": [\"29615403\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct targets linking SOX11 to BTK activation not pinpointed\", \"Cooperating lesions for full malignancy not defined\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extended SOX11 from neural roles to organ morphogenesis, linking it to human CAKUT and identifying direct regulation of a protocadherin B locus control region.\",\n      \"evidence\": \"Sox11 knockout mouse, ChIP, patient variant transactivation analysis\",\n      \"pmids\": [\"29459093\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Effector genes downstream of protocadherin regulation in kidney unclear\", \"Penetrance of human variant not established\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Established a cytoskeletal output for SOX11 by showing it, with SOX4, directly activates FSCN1 to drive cell motility in epidermal wound re-epithelialization.\",\n      \"evidence\": \"Mouse knockouts, ChIP, expression profiling, wound-healing assays\",\n      \"pmids\": [\"31492871\", \"24310815\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the same motility program operates in tumors not directly tested\", \"Division of labor between SOX11 and SOX4 unresolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Provided the structural mechanism for SOX11 pioneer activity, showing HMG-domain binding to nucleosomal DNA distorts DNA and increases accessibility.\",\n      \"evidence\": \"Cryo-EM structures of SOX11 HMG domain on nucleosomes\",\n      \"pmids\": [\"32350470\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How TAD and PTMs feed back on nucleosome engagement not shown\", \"Genome-wide pioneer targeting rules not derived from structure\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defined post-translational control of SOX11 abundance and localization, with USP11 stabilizing the protein and S30 phosphorylation / K91 SUMOylation gating nuclear access and axon-growth programs.\",\n      \"evidence\": \"Usp11 knockout mouse and Co-IP; mass spectrometry and phospho/SUMO site mutants with localization and optic-nerve regeneration readouts\",\n      \"pmids\": [\"33579706\", \"29973868\", \"33441400\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinases and SUMO E3 ligases acting on SOX11 not identified\", \"Crosstalk among phosphorylation, SUMOylation and ubiquitination unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Positioned SOX11 atop chromatin regulation by showing it acts as a core regulatory circuitry factor directly governing SWI/SNF, NuRD and PRC1 components in adrenergic neuroblastoma.\",\n      \"evidence\": \"ChIP-seq, super-enhancer and dependency analysis in neuroblastoma cell lines\",\n      \"pmids\": [\"36882421\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of regulating each chromatin complex not dissected\", \"Whether this circuitry generalizes beyond neuroblastoma unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SOX11's pioneer activity, transactivation domain, and post-translational modifications are integrated to select context-specific target gene sets across neurons, epithelia, and tumors remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No unified model linking PTM state to genomic target choice\", \"Coactivator/corepressor complexes recruited by the TAD largely unidentified\", \"Determinants of oncogenic vs. tumor-suppressive output across tissues unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 4, 5, 6, 17, 28, 32, 34]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [1, 26, 32]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [12, 14]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 4, 34]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [1, 28, 18]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [9, 10, 11, 31, 32, 33]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [4, 5, 6, 24]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [2, 9, 20]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"USP11\", \"WT1\", \"CCND1\", \"HSP90AA1\", \"CTNNB1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}