Affinage

SOX4

Transcription factor SOX-4 · UniProt Q06945

Length
474 aa
Mass
47.3 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOX4 is a sequence-specific transcription factor that binds DNA through its HMG box and activates transcription via a conserved C-terminal transactivation domain shared with the SoxC family, functioning as a context-dependent activator or repressor that orchestrates cell proliferation, differentiation, and migration programs across many tissues (PMID:18403418, PMID:30661772). De novo missense variants in its HMG DNA-binding domain abolish DNA binding and transactivation, causing a neurodevelopmental syndrome and establishing loss of DNA-binding activity as a pathogenic mechanism (PMID:30661772). Mechanistically, SOX4 directs transcription both by recruiting chromatin-modifying machinery and by acting as a pioneer factor: it partners with SMARCA4 to maintain open chromatin at TGFBR2 to sustain PI3K/Akt signaling (PMID:33837205), forms a co-repressor complex with EZH2 and HDAC3 to silence loci such as miR-31 through H3K27me3 (PMID:25644061), and in adult liver binds and closes hepatocyte regulatory sequences before opening biliary regulatory sequences to drive hepatobiliary metaplasia (PMID:38409161). A recurrent theme is SOX4's position downstream of TGF-β signaling, where it is required for TGF-β-induced epithelial-mesenchymal transition and mesenchymal gene expression, cooperating with partners including MTA1 and EZH2 and acting through targets such as TMEM2 and FSCN1 (PMID:22787120, PMID:23301048, PMID:31811272, PMID:27328729, PMID:31492871). SOX4 integrates with Wnt signaling by stabilizing beta-catenin and enhancing beta-catenin/TCF transcriptional output (PMID:17875931, PMID:21165564), and stabilizes p53 by blocking Mdm2-mediated ubiquitination while promoting p300/CBP-dependent p53 acetylation (PMID:19234109). Beyond protein-coding gene control, SOX4 represses a subset of RNA polymerase III-transcribed tRNA genes by impeding TBP and Pol III recruitment (PMID:32123087). In vivo, SOX4 governs diverse differentiation and homeostatic programs, including beta-cell proliferation via direct Cdkn1a repression and insulin secretion via STXBP6 (PMID:28495880, PMID:26993066), pro-B cell survival, iNKT, Treg, and thymic tuft cell development (PMID:23345330, PMID:30287480, PMID:32319705, PMID:34687536), intestinal tuft and enteroendocrine lineage allocation (PMID:30055169), and beige adipocyte thermogenesis through a PPARγ/PRDM16 coactivator complex (PMID:36451857). SOX4 expression is itself tightly controlled post-transcriptionally by m6A modification, where METTL14/YTHDF2 promote SOX4 mRNA decay and METTL3/YTHDF3 promote SOX4 mRNA stability (PMID:32552762, PMID:38195035).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2007 High

    Established that SOX4 is not just a DNA-binding factor but an active modulator of Wnt signaling, linking it to beta-catenin/TCF transcriptional output and proliferation.

    Evidence Gain/loss-of-function, reciprocal Co-IP and reporter assays in SW480 colon carcinoma cells

    PMID:17875931

    Open questions at the time
    • Mechanism of beta-catenin stabilization not resolved here
    • Direct vs. indirect TCF/LEF cooperation on chromatin unclear
  2. 2008 High

    Defined the structural basis of SOX4 transactivation by mapping a conserved 33-residue C-terminal TAD shared across SoxC proteins, explaining differential activation strength.

    Evidence Deletion mutagenesis, reporter transactivation, and TAD structural analysis

    PMID:18403418

    Open questions at the time
    • Coactivators recruited by the TAD not identified
    • No structure of full-length DNA-bound SOX4
  3. 2009 High

    Showed SOX4 feeds into the DNA-damage response by stabilizing p53, positioning it as a tumor-suppressive node in some contexts.

    Evidence Co-IP, ubiquitination assays, apoptosis/cell cycle assays in cell lines and tumorigenesis models

    PMID:19234109

    Open questions at the time
    • Reconciliation with SOX4's oncogenic roles in other tissues unresolved
    • Direct interaction interface with p53/Mdm2 not mapped
  4. 2012 High

    Identified SOX4 as a required effector of TGF-β-induced EMT and an oncogenic cooperator with Ras, defining its core role in mesenchymal transition.

    Evidence Ectopic overexpression, shRNA knockdown, xenografts, TGF-β pathway assays in mammary epithelial cells

    PMID:22787120 PMID:23301048

    Open questions at the time
    • SOX4 alone induces mesenchymal markers but not full EMT
    • Direct EMT target genes only partially defined
  5. 2013 High

    Demonstrated SOX4 is essential for pro-B cell survival via Src/Bcl2, extending its role from cancer EMT to immune cell development.

    Evidence Conditional Sox4 knockout mice with Bcl2 transgene rescue and apoptosis assays

    PMID:23345330

    Open questions at the time
    • Direct SOX4 target genes upstream of Bcl2 not defined
    • Partial rescue indicates additional survival effectors
  6. 2013 High

    Established direct promoter-level target gene control in a differentiation program by showing SOX4 activates Cald1 to drive myoblast fusion.

    Evidence Gel shift, promoter analysis, knockdown/overexpression with caldesmon rescue in C2C12 and embryonic muscle

    PMID:24046453

    Open questions at the time
    • Cofactors at the Cald1 promoter unknown
  7. 2015 High

    Revealed that SOX4 represses targets through recruitment of chromatin-silencing machinery, forming an EZH2/HDAC3 co-repressor complex.

    Evidence Co-IP, ChIP, methylation studies and invasion assays in esophageal cancer cells

    PMID:25644061

    Open questions at the time
    • Determinants of activator vs. repressor mode not defined
    • miR-31/SOX4 feedback dynamics in vivo unclear
  8. 2016 High

    Connected SOX4 to insulin secretion, showing it restricts hormone release by upregulating STXBP6 to promote kiss-and-run exocytosis.

    Evidence Mutant Sox4 mouse, single-granule exocytosis measurements, STXBP6 siRNA rescue, human islets

    PMID:26993066

    Open questions at the time
    • Whether STXBP6 is a direct SOX4 transcriptional target not established
  9. 2017 High

    Showed SOX4 enables facultative beta-cell proliferation through direct repression of the cell-cycle inhibitor Cdkn1a, with diabetes resulting from its loss.

    Evidence Inducible beta-cell-specific Sox4 knockout mice with Cdkn1a expression analysis

    PMID:28495880

    Open questions at the time
    • Direct SOX4 binding at Cdkn1a not shown here
  10. 2017 Medium

    Demonstrated context-dependent repressor activity in development, with SOX4 repressing Sox9 via the TESCO enhancer to influence gonad and germ cell differentiation.

    Evidence Sox4 conditional knockout mice and TESCO reporter assays

    PMID:28118982

    Open questions at the time
    • Cofactors enabling repression at TESCO unknown
    • Single lab
  11. 2018 High

    Established SOX4 as a lineage allocation factor in the intestine, driving tuft/enteroendocrine fates independently of Atoh1.

    Evidence Conditional KO mice, organoids, scRNA-seq, helminth infection, Atoh1 epistasis

    PMID:30055169 PMID:30287480

    Open questions at the time
    • Direct SOX4 target genes for tuft fate not fully mapped
  12. 2019 Medium

    Mapped SOX4 into upstream regulatory cascades (MTA1, ERG, C-MYC) and identified migration targets (FSCN1) in wound repair and cancer.

    Evidence ChIP, Co-IP, knockdown/overexpression in wound, prostate and multiple cancer models

    PMID:24435928 PMID:31238254 PMID:31492871 PMID:31560094 PMID:31811272

    Open questions at the time
    • Direct vs. indirect placement in cascades varies by study
    • Most are single-lab epistasis
  13. 2019 High

    Defined the pathogenic mechanism of SOX4-linked neurodevelopmental disease as loss of DNA binding by HMG-domain missense variants.

    Evidence Trio exome sequencing, in vitro DNA binding/transactivation assays, Xenopus knockdown

    PMID:30661772

    Open questions at the time
    • Critical neural target genes driving the syndrome unknown
  14. 2020 High

    Uncovered an unexpected Pol III-directed function, with SOX4 repressing specific tRNA genes by blocking TBP/Pol III recruitment.

    Evidence Genome-wide ChIP-seq, CRISPR tRNAi knockdown and rescue in glioblastoma cells

    PMID:32123087

    Open questions at the time
    • How an HMG factor docks at tRNA loci to exclude Pol III machinery not structurally defined
  15. 2020 High

    Showed SOX4 expression is governed post-transcriptionally by m6A, with METTL14/YTHDF2 promoting SOX4 mRNA decay.

    Evidence MeRIP-seq, RIP, METTL14 knockdown/overexpression and YTHDF2 assays

    PMID:32552762

    Open questions at the time
    • Signals controlling m6A deposition on SOX4 mRNA unknown
  16. 2020 High

    Extended SOX4's TGF-β axis to immune evasion and Treg function, controlling immune gene programs and CD39 expression.

    Evidence SOX4 inactivation, integrin blockade, murine TNBC models; CRISPR KO/overexpression in Treg

    PMID:32319705 PMID:33385331

    Open questions at the time
    • Direct immune-gene targets of SOX4 not fully mapped
    • CD39 directness not established
  17. 2021 High

    Established SOX4 as a chromatin-remodeling partner of SMARCA4 that maintains accessibility at TGFBR2 to sustain PI3K/Akt signaling.

    Evidence Co-IP, ChIP, ATAC-seq and TGFBR2 rescue in triple-negative breast cancer

    PMID:33837205

    Open questions at the time
    • Whether SMARCA4 recruitment is direct via SOX4 not resolved
  18. 2022 High

    Defined SOX4's co-regulator partnerships in physiology: a PPARγ/PRDM16 thermogenic complex in adipocytes and chromatin co-binding with RELA in inflammation.

    Evidence Adipocyte-specific KO, Co-IP, ChIP, calorimetry; ChIP-seq/RNA-seq/Co-IP in synoviocytes

    PMID:35529852 PMID:36451857

    Open questions at the time
    • Determinants of SOX4-RELA co-binding selectivity unclear
  19. 2022 High

    Showed SOX4 stabilizes the progesterone receptor by repressing HERC4-mediated degradation, a non-transcriptional protein-stability role required for decidualization.

    Evidence ChIP-seq, RNA-seq, IP-MS and decidualization assays in endometrial stromal cells

    PMID:35244538

    Open questions at the time
    • How SOX4 represses HERC4 mechanistically not fully defined
  20. 2024 High

    Demonstrated bona fide pioneer factor activity, with SOX4 sequentially closing hepatocyte and opening biliary regulatory chromatin to drive metaplasia.

    Evidence Lineage tracing, ATAC-seq, ChIP-seq with SOX4 overexpression in adult liver

    PMID:38409161

    Open questions at the time
    • Cofactors enabling the close-then-open transition unknown
  21. 2024 High

    Linked SOX4 to a second m6A regulatory mode (METTL3/YTHDF3-stabilized) and to EZH2-driven ferroptosis and BMI1-driven angiogenesis programs.

    Evidence MeRIP-seq/RIP with in vivo rescue; ChIP and KO/inhibitor studies in osteoblast, kidney and NSCLC models

    PMID:38169402 PMID:38195035 PMID:39349443

    Open questions at the time
    • Tissue-specific switch between stabilizing and destabilizing m6A readers not resolved
    • EZH2/BMI1 axes partly single-lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • What molecular determinants switch SOX4 between activator, repressor, and pioneer modes, and how cofactor choice is dictated across tissues, remains unresolved.
  • No structure of SOX4 bound to DNA with a cofactor
  • Rules governing activator vs. repressor recruitment undefined
  • Generality of pioneer activity beyond liver untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3 R-HSA-8953854 Metabolism of RNA 3
Partners
CTNNB1EZH2PPARGPRDM16RELASMARCA4TCF/LEFTP53
Complex memberships
PPARγ-PRDM16-SOX4 thermogenic complexSOX4-EZH2-HDAC3 co-repressor complexSOX4-SMARCA4 chromatin complex

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 SOX4 enhances beta-catenin/TCF activity and proliferation of SW480 colon carcinoma cells; SOX4 physically interacts with TCF/LEF family members via its HMG box domain and may function to stabilize beta-catenin protein, in contrast to SOX17 which promotes proteasome-dependent degradation of beta-catenin and TCF. Gain- and loss-of-function assays, co-immunoprecipitation, luciferase reporter assay, proteasome inhibitor experiments in SW480 cells Molecular and cellular biology High 17875931
2008 SOX4 (and SOX11, SOX12) share a conserved C-terminal transactivation domain (TAD) consisting of the last 33 residues; this TAD is required for transcriptional activation, and acidic domains interfere with DNA binding. SOX4's TAD activates transcription less efficiently than SOX11 due to less stable alpha-helical structure. Deletion mutagenesis, reporter gene transactivation assays, structural analysis of TAD Nucleic acids research High 18403418
2009 SOX4 is induced by DNA damage, interacts with p53 protein, blocks Mdm2-mediated p53 ubiquitination and degradation thereby stabilizing p53, and enhances p53 acetylation by facilitating formation of a p300/CBP/p53 complex. These activities promote cell cycle arrest and apoptosis in a p53-dependent manner. Co-immunoprecipitation, ubiquitination assays, apoptosis/cell cycle assays, gain/loss-of-function in cell lines and in vivo tumorigenesis models Proceedings of the National Academy of Sciences of the United States of America High 19234109
2010 SOX4 stabilizes beta-catenin protein (without inducing its transcription) by inducing CK2 expression, thereby enhancing beta-catenin/TCF activity and cyclin D1 levels in a dose-dependent manner. SOX4 overexpression and siRNA knockdown, western blot, luciferase reporter assay Oncology reports Medium 21165564
2012 SOX4 overexpression in immortalized mammary epithelial cells is sufficient to induce EMT and activate the TGF-β pathway; SOX4 is required for TGF-β-induced EMT, and cooperates with oncogenic Ras to promote tumorigenesis in vivo. Ectopic overexpression, shRNA knockdown, xenograft mouse models, TGF-β pathway assays Cancer research High 22787120
2012 SOX4 positively regulates Dicer expression by binding to the Dicer promoter and enhancing its transcriptional activity, thereby suppressing melanoma cell invasion through regulation of miRNA biogenesis. Promoter binding assay (gel mobility shift), luciferase reporter assay, shRNA knockdown, Matrigel invasion assay, tissue microarray Oncogene Medium 22689055
2013 SOX4 mediates TGF-β-induced expression of mesenchymal markers (N-cadherin, vimentin, fibronectin) in human mammary epithelial cells; conditional activation of SOX4 is sufficient to induce these markers but not complete EMT (no change in E-cadherin or beta-catenin); shRNA-mediated knockdown of SOX4 significantly delays TGF-β-induced mesenchymal gene expression. Conditional SOX4 activation system, shRNA knockdown, qRT-PCR, western blot PloS one Medium 23301048
2013 SOX4 is required for the survival of pro-B cells; SOX4-deficient pro-B cells undergo apoptosis, show decreased activation of Src downstream of c-Kit, and have reduced Bcl2 levels. Restoration of Bcl2 partially rescues pro-B cell survival and B cell maturation in the absence of Sox4. Conditional Sox4 knockout mice, flow cytometry, apoptosis assays, Bcl2 transgene rescue experiment Journal of immunology High 23345330
2013 SOX4 promotes skeletal myoblast differentiation by transcriptionally activating caldesmon (Cald1) expression; Sox4 binds to the Cald1 promoter; knockdown of Sox4 reduces caldesmon synthesis and myoblast fusion, while overexpression of caldesmon in Sox4-silenced cells rescues differentiation. Promoter analysis, gel mobility shift assay, siRNA knockdown, overexpression, C2C12 differentiation assays, mouse embryonic muscle experiments Journal of cell science High 24046453
2014 ERG transcriptionally regulates SOX4 expression via binding to its promoter; ERG and SOX4 physically interact and cooperate in TGF-β1-induced EMT in prostate cancer cells. TGF-β1 increases active chromatin marks (H3K4me3, H4K16ac) and decreases H3K27me3 at ERG and SOX4 promoters. Co-immunoprecipitation, ChIP assay, siRNA knockdown, EMT functional assays The Prostate Medium 24435928
2015 SOX4 promotes esophageal cancer cell invasion by forming a co-repressor complex with EZH2 and HDAC3 that binds the miR-31 promoter, silencing miR-31 through H3K27me3 and histone deacetylation; miR-31 in turn targets SOX4 mRNA for degradation, creating a feedback loop. Co-immunoprecipitation, ChIP assay, methylation studies, overexpression and shRNA knockdown, migration/invasion assays Molecular cancer High 25644061
2016 SOX4 directly transcriptionally activates TMEM2; TMEM2 mediates SOX4-dependent pro-invasive and pro-migratory effects and metastatic colonization in breast cancer cells. Systematic genomic/molecular approach, ChIP-seq, functional invasion/migration assays, gain/loss-of-function Cancer research Medium 27328729
2016 Increased SOX4 expression reduces insulin secretion by increasing kiss-and-run exocytosis (fusion pore restricted to ~2 nm diameter, preventing insulin exit) through upregulation of STXBP6; silencing STXBP6 reverses the SOX4-mediated inhibition of hormone release. Mutant Sox4 mouse model, single-granule exocytosis measurements, microarray, SOX4 overexpression in EndoC-βH2 cells, STXBP6 siRNA rescue, human islet preparations (n=63) Diabetes High 26993066
2017 SOX4 allows facultative beta-cell proliferation through direct repression of Cdkn1a (p21); Sox4 conditional knockout mice develop progressive diabetes due to reduced beta-cell proliferation caused by Cdkn1a induction. Inducible beta-cell-specific Sox4 knockout mouse model, immunostaining for beta-cell mass, gene expression analysis, Cdkn1a regulation studies Diabetes High 28495880
2017 SOX4 transcriptionally upregulates the miR-17-92 cluster in prostate cancer cells, which in turn downregulates RB1 protein expression, promoting cell proliferation, migration, invasion, and neuroendocrine phenotype. High-throughput miRNA profiling, ChIP/luciferase assays for SOX4 binding to miR-17-92 locus, functional knockdown studies Neoplasia Medium 31238254
2017 SOX4 directly binds ADAMTS4 and Adamts5 gene promoters and up-regulates their expression in chondrogenic cells; overexpression of Sox4 via adenovirus in mouse femoral head cartilage organ cultures causes articular cartilage destruction with increased Adamts5 expression. Luciferase reporter assay, ChIP assay, adenovirus-mediated overexpression, organ culture experiments FASEB journal High 30016600
2017 SOX4 represses Sox9 transcription via the upstream testis-specific enhancer core (TESCO) element in fetal gonads, acting as a transcriptional repressor in a context-dependent manner. Sox4 deficiency results in elongated gonads, increased testis cords, and impaired male germ cell differentiation markers (reduced Nanos2 and Dnmt3l). Sox4 conditional knockout mice, reporter assays with TESCO element, gene expression profiling Developmental biology Medium 28118982
2018 SOX4 controls iNKT cell differentiation in the thymus by inducing MicroRNA-181 (Mir181) expression to enhance TCR signaling and Ca2+ fluxes in iNKT precursors. Genetic analysis, miRNA profiling, Ca2+ flux assays, gain/loss-of-function in developing thymocytes The Journal of experimental medicine Medium 30287480
2018 Sox4 promotes tuft and enteroendocrine cell lineage allocation in the intestine independently of Atoh1; Sox4 conditional knockout mice show impaired ISC function and reduced tuft/enteroendocrine cell numbers; overexpression of Sox4 is sufficient to induce tuft and enteroendocrine differentiation even in the absence of Atoh1. Sox4 conditional intestinal-specific knockout mice, organoids, single-cell RNA-seq, IL-13 stimulation, helminth infection model, Atoh1 inducible KO organoids with SOX4 overexpression Gastroenterology High 30055169
2019 SOX11 and SOX4 drive reactivation of an embryonic gene program during wound repair; SOX4 directly targets FSCN1 (fascin) to regulate cell migration; deficiency of Sox11 and Sox4 accelerates differentiation and dramatically impairs cell motility and re-epithelialization. Mouse wound model, Sox4/Sox11 deficiency studies, ChIP, gene expression analysis, cell motility assays Nature communications High 31492871
2019 MTA1 acts upstream of SOX4 in TGF-β-mediated EMT; a TGF-β-MTA1-SOX4-EZH2 signaling cascade drives EMT, where SOX4 is required for both MTA1-driven and TGF-β-driven EMT, and EZH2 is a critical downstream responsive gene of this axis. Gene expression profiling, shRNA knockdown, overexpression in multiple cancer cell lines, TCGA/cDNA microarray validation Oncogene Medium 31811272
2019 C-MYC transcriptionally activates SOX4 by binding to its promoter; C-MYC and SOX4 proteins physically interact in prostate cancer cells. ChIP assay, luciferase reporter assay, Co-immunoprecipitation Medical oncology Medium 31560094
2019 De novo heterozygous missense variants in the HMG DNA-binding domain of SOX4 cause a neurodevelopmental syndrome; these variant proteins are unable to bind DNA in vitro and fail to transactivate SOX reporter genes in cultured cells, establishing loss of DNA-binding activity as the pathogenic mechanism. Trio-based exome sequencing, in vitro DNA binding assays, luciferase reporter transactivation assays, Xenopus sox4 knockdown American journal of human genetics High 30661772
2020 METTL14-mediated m6A modification of SOX4 mRNA promotes its degradation via the YTHDF2-dependent pathway; knockdown of METTL14 abolishes SOX4 mRNA m6A modification and elevates SOX4 mRNA expression. MeRIP-Seq, RNA immunoprecipitation, METTL14 knockdown/overexpression, YTHDF2 pathway assays Molecular cancer High 32552762
2020 SOX4 expression is regulated by the integrin αvβ6 receptor on TNBC cells, which activates TGF-β from a latent precursor; this integrin αvβ6-TGF-β-SOX4 pathway drives immune evasion. Inactivation of SOX4 increases expression of innate and adaptive immune pathway genes; an integrin αvβ6/8-blocking monoclonal antibody inhibits SOX4 expression. SOX4 inactivation in tumor cells, gene expression profiling, integrin blocking antibody, murine TNBC models Cancer cell High 33385331
2020 SOX4 directly controls expression of a subset of tRNA genes (including tRNAi) via RNA polymerase III; SOX4 binds specific tRNA gene loci (identified by ChIP-seq) and impedes recruitment of TATA box binding protein and Pol III, thereby repressing tRNA expression and inhibiting cell proliferation in glioblastoma cells. ChIP-seq (genome-wide SOX4 binding), CRISPR/Cas9 tRNAi knockdown, ectopic tRNAi rescue, glioblastoma proliferation assays Proceedings of the National Academy of Sciences of the United States of America High 32123087
2020 TGF-β mediates upregulation of CD39 expression on regulatory T cells via SOX4 as a downstream transcription factor; overexpression of SOX4 in Treg strongly increases CD39 expression, and CRISPR/Cas9-mediated knockout of SOX4 in Treg decreases CD39 expression. SOX4 overexpression, CRISPR/Cas9 knockout in Treg, flow cytometry, TGF-β/mTOR pathway assays FASEB journal Medium 32319705
2021 SOX4 and SMARCA4 form a complex required to maintain open chromatin at TGFBR2 regulatory regions; this SOX4-SMARCA4 complex directly transcriptionally activates TGFBR2, which is required for SOX4-dependent PI3K/Akt signaling in triple-negative breast cancer. Co-immunoprecipitation, ChIP assay, ATAC-seq/chromatin accessibility assay, TGFBR2 knockdown rescue, genomic/proteomic analyses NPJ breast cancer High 33837205
2021 CRISPR/Cas9-mediated loss of SOX4 in mammary tumor organoids inhibits differentiation by regulating a subset of fetal mammary stem cell (fMaSC) genes; SOX4 is required for maintaining tumor cells in an undifferentiated and proliferative state, and its loss impairs primary tumor growth and metastatic outgrowth. CRISPR/Cas9 knockout in PyMT mouse mammary organoids, RNA-seq, in vivo tumor growth assays, competitive growth experiments Oncogene High 34584219
2022 SOX4 directly regulates FOXO1 expression (established by genome-wide SOX4 chromatin binding assay and RNA-seq) and modulates progesterone receptor (PGR) stability by repressing E3 ubiquitin ligase HERC4-mediated degradation, as identified by immunoprecipitation and mass spectrometry; this SOX4-HERC4-PGR axis is required for human endometrial stromal cell decidualization. Genome-wide ChIP-seq (SOX4 binding), RNA-seq, immunoprecipitation, mass spectrometry, functional decidualization assays eLife High 35244538
2022 SOX4 and RELA/p65 physically interact on chromatin; ChIP-seq reveals 70.4% of SOX4 peak summits are within 50 bp of RELA peak summits; together they co-operatively regulate TNF-responsive genes including inflammation mediators, histone remodeling enzymes and AP-1 pathway components in fibroblast-like synoviocytes. An autoregulatory mode involves TNF-mediated switch from RELA to SOX4 binding in the 3′ UTR of Sox4 and Sox11. ChIP-seq, RNA-seq from SoxC-knockout FLS, co-immunoprecipitation Frontiers in immunology High 35529852
2022 SOX4 promotes beige adipocyte thermogenesis by binding PPARγ as a coactivator, and recruiting PRDM16 to PPARγ to form a transcriptional complex that elevates thermogenic gene (including Ucp1) expression; adipocyte-specific or UCP1+ cell-specific deletion of SOX4 causes cold intolerance, decreased energy expenditure, obesity, and impaired thermogenic gene expression. Adipocyte-specific conditional KO mice (two models), endogenous and exogenous Co-IP, ChIP-qPCR, FAIRE assay, luciferase reporter assays, indirect calorimetry Theranostics High 36451857
2022 SOX4 is required for thymic tuft cell development; Sox4 deficiency specifically in thymic epithelial cells markedly reduces thymic tuft cells without affecting Aire+ or Ccl21a+ mTEC subsets; LTβR acts upstream of Sox4 in this differentiation axis. TEC-specific Sox4 conditional knockout mice, flow cytometry, genetic epistasis with LTβR-deficient mice International immunology High 34687536
2022 METTL3-mediated m6A modification of SOX4 mRNA at CDS regions promotes SOX4 mRNA stability and expression; YTHDF3 is the m6A reader that recognizes modified SOX4 mRNA and modulates its stability/protein levels; this axis regulates osteoblast proliferation and differentiation. MeRIP-seq, RNA-seq, RIP assay (confirming METTL3-SOX4 interaction), YTHDF3 knockdown, METTL3 knockdown/OVX mouse model with AAV2-SOX4 rescue Cellular signalling High 38195035
2024 SOX4 acts as a pioneer factor in adult mouse liver: it initially directly binds and closes hepatocyte regulatory sequences via an overlapping motif with HNF4A (a hepatocyte master regulator), and subsequently exerts pioneer factor activity to open biliary regulatory sequences, thereby initiating hepatobiliary metaplasia. Lineage tracing, ATAC-seq (chromatin accessibility), ChIP-seq, SOX4 overexpression in adult liver, timing of chromatin opening vs. closing Nature communications High 38409161
2024 SOX4 directly modulates EZH2 expression, which in turn suppresses SLC7A11 through H3K27me3, driving ferroptosis in calcium oxalate crystal-induced kidney injury; the SOX4/EZH2/SLC7A11 axis was confirmed by ChIP assay. RNA-seq, single-nucleus RNA-seq, ChIP assay, EZH2 KO and inhibitor studies, in vitro and in vivo CaOx models Journal of translational medicine Medium 38169402
2015 SOX4 expression is required for Schwann cell myelination; transgenic overexpression of Sox4 in Schwann cells causes a temporary delay in PNS myelination without affecting axonal sorting, and aggravates neuropathic phenotype in a Charcot-Marie-Tooth 4C model. Sox4 protein expression in Schwann cells is strictly post-transcriptionally regulated despite mRNA overexpression. Transgenic Sox4 overexpression in Schwann cells, myelination analysis, CMT4C mouse model, western blot protein analysis The European journal of neuroscience Medium 25899854
2015 SOX4 directly binds to the SOX4 binding motif in the Cyr61 proximal promoter and up-regulates Cyr61 (an extracellular matrix-associated signaling protein) expression in colon cancer cells; knockdown of Sox4 reduces Cyr61 expression. PCR-based microarray, siRNA knockdown, luciferase reporter assay, ChIP assay Cellular physiology and biochemistry Medium 25059387
2018 FHL3 interacts with the Smad2/3 protein complex at the SOX4 promoter region, inhibits SOX4 transcriptional activity by recruiting PPM1A phosphatase to Smad2/3, and thereby suppresses glioma stem cell (GSC) self-renewal via downregulation of SOX2. Co-immunoprecipitation, ChIP assay, promoter reporter assay, sphere formation assay, in vivo tumor model Cell death and differentiation Medium 29955125
2020 SOX4 directly binds to the promoter of the Anillin gene and activates its transcription; SP1 acts as an upstream activator of SOX4; this SOX4-Anillin axis facilitates HCC cell proliferation and tumor growth. ChIP assay (SOX4 binding to Anillin promoter), gain/loss-of-function, in vivo tumor model Translational oncology Medium 32645689
2019 MTA1 acts upstream of SOX4 in the TGF-β pathway; both MTA1 and SOX4 are induced by TGF-β and are indispensable for TGF-β-mediated EMT; EZH2 is a critical downstream responsive gene of the TGF-β-MTA1-SOX4 cascade. Gene expression profiling, shRNA knockdown/overexpression in multiple cell lines, TCGA pan-cancer analysis Oncogene Medium 31811272
2024 SOX4 drives NSCLC progression by transcriptionally activating BMI1; SOX4-induced BMI1 promotes ubiquitination of histone H2A (H2Aub), leading to decreased ZNF24 expression, which triggers VEGF-A secretion and promotes angiogenesis in NSCLC. In vitro overexpression/knockdown, ChIP (SOX4 binding to BMI1 promoter), orthotopic in vivo models, functional angiogenesis assays Cell death & disease Medium 39349443

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer. Molecular cancer 328 32552762
2007 Sox17 and Sox4 differentially regulate beta-catenin/T-cell factor activity and proliferation of colon carcinoma cells. Molecular and cellular biology 288 17875931
2012 SOX4 induces epithelial-mesenchymal transition and contributes to breast cancer progression. Cancer research 233 22787120
2008 The three SoxC proteins--Sox4, Sox11 and Sox12--exhibit overlapping expression patterns and molecular properties. Nucleic acids research 214 18403418
2020 Integrin αvβ6-TGFβ-SOX4 Pathway Drives Immune Evasion in Triple-Negative Breast Cancer. Cancer cell 185 33385331
2019 SOX4: The unappreciated oncogene. Seminars in cancer biology 175 31445218
2012 The role of SRY-related HMG box transcription factor 4 (SOX4) in tumorigenesis and metastasis: friend or foe? Oncogene 175 23246969
2006 SOX4 expression in bladder carcinoma: clinical aspects and in vitro functional characterization. Cancer research 140 16585165
2009 Induction of SOX4 by DNA damage is critical for p53 stabilization and function. Proceedings of the National Academy of Sciences of the United States of America 118 19234109
2017 The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia. Molecular cancer 112 28724437
2015 SOX4 interacts with EZH2 and HDAC3 to suppress microRNA-31 in invasive esophageal cancer cells. Molecular cancer 109 25644061
2002 Differential expression of SOX4 and SOX11 in medulloblastoma. Journal of neuro-oncology 100 12125983
2022 Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathway. Journal of experimental & clinical cancer research : CR 90 35513871
2013 SOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition. PloS one 86 23301048
2018 Sox4 Promotes Atoh1-Independent Intestinal Secretory Differentiation Toward Tuft and Enteroendocrine Fates. Gastroenterology 83 30055169
2019 A TGF-β-MTA1-SOX4-EZH2 signaling axis drives epithelial-mesenchymal transition in tumor metastasis. Oncogene 78 31811272
2019 SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair. Nature communications 74 31492871
2016 TMEM2 Is a SOX4-Regulated Gene That Mediates Metastatic Migration and Invasion in Breast Cancer. Cancer research 68 27328729
2012 Sox4-mediated Dicer expression is critical for suppression of melanoma cell invasion. Oncogene 61 22689055
2019 LINC01133 inhibits breast cancer invasion and metastasis by negatively regulating SOX4 expression through EZH2. Journal of cellular and molecular medicine 58 31557401
2014 ERG-SOX4 interaction promotes epithelial-mesenchymal transition in prostate cancer cells. The Prostate 56 24435928
2016 Increased Expression of the Diabetes Gene SOX4 Reduces Insulin Secretion by Impaired Fusion Pore Expansion. Diabetes 53 26993066
1993 Characterization and mapping of the human SOX4 gene. Mammalian genome : official journal of the International Mammalian Genome Society 53 8268656
2017 P53-miR-191-SOX4 regulatory loop affects apoptosis in breast cancer. RNA (New York, N.Y.) 51 28450532
2013 Sox4 is required for the survival of pro-B cells. Journal of immunology (Baltimore, Md. : 1950) 50 23345330
2024 The SOX4/EZH2/SLC7A11 signaling axis mediates ferroptosis in calcium oxalate crystal deposition-induced kidney injury. Journal of translational medicine 49 38169402
2018 Sox4 is involved in osteoarthritic cartilage deterioration through induction of ADAMTS4 and ADAMTS5. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 49 30016600
2017 MiR-129-5p Inhibits Proliferation and Invasion of Chondrosarcoma Cells by Regulating SOX4/Wnt/β-Catenin Signaling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 47 28535514
2019 De Novo SOX4 Variants Cause a Neurodevelopmental Disease Associated with Mild Dysmorphism. American journal of human genetics 46 30661772
2020 The TGF-b/SOX4 axis and ROS-driven autophagy co-mediate CD39 expression in regulatory T-cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 45 32319705
2020 SOX4 promotes the growth and metastasis of breast cancer. Cancer cell international 45 33005101
2015 MicroRNA-132 inhibits cell growth and metastasis in osteosarcoma cell lines possibly by targeting Sox4. International journal of oncology 45 26352673
2010 Sox4 stimulates ß-catenin activity through induction of CK2. Oncology reports 44 21165564
2022 SOX4 is a novel phenotypic regulator of endothelial cells in atherosclerosis revealed by single-cell analysis. Journal of advanced research 43 36585108
1999 Expression and hormonal regulation of the Sox4 gene in mouse female reproductive tissues. Biology of reproduction 43 10411530
2017 Amplification of SOX4 promotes PI3K/Akt signaling in human breast cancer. Breast cancer research and treatment 42 28176176
2019 The SOX4/miR-17-92/RB1 Axis Promotes Prostate Cancer Progression. Neoplasia (New York, N.Y.) 39 31238254
2022 SOX4 promotes beige adipocyte-mediated adaptive thermogenesis by facilitating PRDM16-PPARγ complex. Theranostics 37 36451857
2016 Increased expression of SOX4 is associated with colorectal cancer progression. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 26768610
2022 SOX4 facilitates PGR protein stability and FOXO1 expression conducive for human endometrial decidualization. eLife 36 35244538
2017 Overexpression of SOX4 promotes cell migration and invasion of renal cell carcinoma by inducing epithelial-mesenchymal transition. International journal of oncology 36 28534986
2014 SOX4 inhibits GBM cell growth and induces G0/G1 cell cycle arrest through Akt-p53 axis. BMC neurology 36 25366337
2017 SOX4 induces tumor invasion by targeting EMT-related pathway in prostate cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 35 28466783
2015 Down-regulated SOX4 expression suppresses cell proliferation, metastasis and induces apoptosis in Xuanwei female lung cancer patients. Journal of cellular biochemistry 35 25565486
2020 lncRNA XIST promotes glioma proliferation and metastasis through miR-133a/SOX4. Experimental and therapeutic medicine 34 32104215
2017 SOX4 regulates gonad morphogenesis and promotes male germ cell differentiation in mice. Developmental biology 34 28118982
2023 WNT2-SOX4 positive feedback loop promotes chemoresistance and tumorigenesis by inducing stem-cell like properties in gastric cancer. Oncogene 33 37634009
2017 SOX4 promotes melanoma cell migration and invasion though the activation of the NF-κB signaling pathway. International journal of molecular medicine 33 28627651
2015 Sox4 Expression Confers Bladder Cancer Stem Cell Properties and Predicts for Poor Patient Outcome. International journal of biological sciences 33 26681916
2018 SOX4 controls invariant NKT cell differentiation by tuning TCR signaling. The Journal of experimental medicine 32 30287480
2022 Circular RNA drives resistance to anti-PD-1 immunotherapy by regulating the miR-30a-5p/SOX4 axis in non-small cell lung cancer. Cancer drug resistance (Alhambra, Calif.) 31 35800365
2015 Upregulated Expression of SOX4 Is Associated with Tumor Growth and Metastasis in Nasopharyngeal Carcinoma. Disease markers 31 26578818
2020 SOX4-mediated repression of specific tRNAs inhibits proliferation of human glioblastoma cells. Proceedings of the National Academy of Sciences of the United States of America 29 32123087
2019 SOX4 is activated by C-MYC in prostate cancer. Medical oncology (Northwood, London, England) 29 31560094
2020 Long Non-coding RNA H19 Regulates Porcine Satellite Cell Differentiation Through miR-140-5p/SOX4 and DBN1. Frontiers in cell and developmental biology 26 33324629
2018 FHL3 links cell growth and self-renewal by modulating SOX4 in glioma. Cell death and differentiation 26 29955125
2017 SOX4 Allows Facultative β-Cell Proliferation Through Repression of Cdkn1a. Diabetes 26 28495880
2020 MiR-34c downregulation leads to SOX4 overexpression and cisplatin resistance in nasopharyngeal carcinoma. BMC cancer 24 32586280
2015 Estrogen induces androgen-repressed SOX4 expression to promote progression of prostate cancer cells. The Prostate 24 26015225
2003 Conservation of Sox4 gene structure and expression during chicken embryogenesis. Gene 24 14597385
2024 Cellular reprogramming in vivo initiated by SOX4 pioneer factor activity. Nature communications 23 38409161
2021 THAP9-AS1/miR-133b/SOX4 positive feedback loop facilitates the progression of esophageal squamous cell carcinoma. Cell death & disease 23 33854048
2021 LncRNA SNHG17 regulates cell proliferation and invasion by targeting miR-338-3p/SOX4 axis in esophageal squamous cell carcinoma. Cell death & disease 23 34429400
2021 ROS/TGF-β signal mediated accumulation of SOX4 in OA-FLS promotes cell senescence. Experimental gerontology 23 34742854
2024 METTL3-mediated m6A modification of SOX4 regulates osteoblast proliferation and differentiation via YTHDF3 recognition. Cellular signalling 22 38195035
2024 SOX4-BMI1 axis promotes non-small cell lung cancer progression and facilitates angiogenesis by suppressing ZNF24. Cell death & disease 22 39349443
2022 SOX4-activated lncRNA MCM3AP-AS1 aggravates osteoarthritis progression by modulating miR-149-5p/Notch1 signaling. Cytokine 22 35202986
2015 SOX4 expression is associated with treatment failure and chemoradioresistance in oral squamous cell carcinoma. BMC cancer 22 26555193
2021 SOX4 and SMARCA4 cooperatively regulate PI3k signaling through transcriptional activation of TGFBR2. NPJ breast cancer 21 33837205
2020 Anillin facilitates cell proliferation and induces tumor growth of hepatocellular carcinoma via miR-138/SOX4 axis regulation. Translational oncology 21 32645689
2013 Expression of Sox4 and Sox11 is regulated by multiple mechanisms during retinal development. FEBS letters 21 23313252
2024 ALKBH5-mediated m6A modification of circFOXP1 promotes gastric cancer progression by regulating SOX4 expression and sponging miR-338-3p. Communications biology 20 38745044
2021 LncRNA SNHG5 promotes cervical cancer progression by regulating the miR-132/SOX4 pathway. Autoimmunity 20 33622094
2021 Regulation of a progenitor gene program by SOX4 is essential for mammary tumor proliferation. Oncogene 20 34584219
2017 Upregulation of MiR-369-3p suppresses cell migration and proliferation by targeting SOX4 in Hirschsprung's disease. Journal of pediatric surgery 20 28412032
2023 The ALKBH5/SOX4 axis promotes liver cancer stem cell properties via activating the SHH signaling pathway. Journal of cancer research and clinical oncology 19 37646828
2019 MicroRNA-625 inhibits cell invasion and epithelial-mesenchymal transition by targeting SOX4 in laryngeal squamous cell carcinoma. Bioscience reports 19 30563928
2013 Sox4-mediated caldesmon expression facilitates differentiation of skeletal myoblasts. Journal of cell science 19 24046453
2023 LINC00926 promotes progression of renal cell carcinoma via regulating miR-30a-5p/SOX4 axis and activating IFNγ-JAK2-STAT1 pathway. Cancer letters 18 37866544
2021 miRNA-214-5p inhibits prostate cancer cell proliferation by targeting SOX4. World journal of surgical oncology 18 34863188
2023 SOX4 is a pivotal regulator of tumorigenesis in differentiated thyroid cancer. Molecular and cellular endocrinology 17 37673293
2022 HOTAIR mediates cisplatin resistance in nasopharyngeal carcinoma by regulating miR-106a-5p/SOX4 axis. Bioengineered 17 35227173
2021 ZFAS1 Promotes Colorectal Cancer Metastasis Through Modulating miR-34b/SOX4 Targeting. Cell biochemistry and biophysics 17 33725330
2022 E2F7 enhances hepatocellular carcinoma growth by preserving the SP1/SOX4/Anillin axis via repressing miRNA-383-5p transcription. Molecular carcinogenesis 16 35924788
2022 SOX4-mediated FBW7 transcriptional upregulation confers Tamoxifen resistance in ER+ breast cancers via GATA3 downregulation. Life sciences 15 35662647
2014 Sox4 up-regulates Cyr61 expression in colon cancer cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 15 25059387
2023 circGRAMD1B contributes to migration, invasion and epithelial-mesenchymal transition of lung adenocarcinoma cells via modulating the expression of SOX4. Functional & integrative genomics 14 36867268
2020 XIST promotes cell proliferation and invasion by regulating miR-140-5p and SOX4 in retinoblastoma. World journal of surgical oncology 14 32127028
2017 DownRegulated SOX4 Expression Suppresses Cell Proliferation, Migration, and Induces Apoptosis in Osteosarcoma In Vitro and In Vivo. Calcified tissue international 14 29038881
2017 Long non-coding RNA Sox4 promotes proliferation and migration by activating Wnt/β-catenin signaling pathway in osteosarcoma. Die Pharmazie 14 29441981
2023 Cancer-associated fibroblasts drive early pancreatic cancer cell invasion via the SOX4/MMP11 signalling axis. Biochimica et biophysica acta. Molecular basis of disease 13 37633471
2022 Consolidation of the clinical and genetic definition of a SOX4-related neurodevelopmental syndrome. Journal of medical genetics 13 35232796
2021 SOX4 as biomarker in hepatitis B virus-associated hepatocellular carcinoma. Journal of Cancer 13 33995626
2021 Multi-Omics Analysis of SOX4, SOX11, and SOX12 Expression and the Associated Pathways in Human Cancers. Journal of personalized medicine 13 34442467
2021 MiR-296-3p inhibits cell proliferation by the SOX4-Wnt/βcatenin pathway in triple-negative breast cancer. Journal of biosciences 13 34785625
2015 Sox4 participates in the modulation of Schwann cell myelination. The European journal of neuroscience 13 25899854
2024 Engineered melatonin-pretreated plasma exosomes repair traumatic spinal cord injury by regulating miR-138-5p/SOX4 axis mediated microglia polarization. Journal of orthopaedic translation 12 39512441
2022 The transcription factor Sox4 is required for thymic tuft cell development. International immunology 12 34687536
2022 SOX4 and RELA Function as Transcriptional Partners to Regulate the Expression of TNF- Responsive Genes in Fibroblast-Like Synoviocytes. Frontiers in immunology 12 35529852
2020 MicroRNA-92a Inhibits the Cell Viability and Metastasis of Prostate Cancer by Targeting SOX4. Technology in cancer research & treatment 12 32930086

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