Affinage

SOX4

Transcription factor SOX-4 · UniProt Q06945

Length
474 aa
Mass
47.3 kDa
Annotated
2026-04-28
100 papers in source corpus 38 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOX4 is an HMG-box transcription factor that functions as a pioneer factor to remodel chromatin and regulate cell fate decisions across diverse developmental and disease contexts, including EMT, immune regulation, endocrine cell differentiation, and thermogenesis. SOX4 directly binds and activates promoters of target genes (EZH2, Cdkn1a, CXCL12, TMEM2, CXCR7, Cald1, ADAMTS4/5, Dicer, WNT2, BMI1) to drive context-dependent transcriptional programs, and can function as a pioneer factor by closing hepatocyte enhancers and opening biliary regulatory sequences to reprogram cell identity (PMID:38409161, PMID:23764001, PMID:27328729). Its transcriptional output is shaped by post-translational modifications—KAT5-mediated acetylation at K95 activates target promoters while HDAC1 antagonizes this switch (PMID:26291311)—and by co-factor interactions including p53/p300 complex stabilization (PMID:19234109), an EZH2/HDAC3 co-repressor complex (PMID:25644061), and a PPARγ/PRDM16 coactivator complex that drives thermogenic gene expression in beige adipocytes (PMID:36451857). De novo heterozygous missense variants in the HMG DNA-binding domain that abolish DNA binding and transactivation cause a neurodevelopmental syndrome (PMID:30661772).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2009 High

    Establishing that SOX4 is not solely a transcriptional activator but also a signaling node that stabilizes p53 by blocking Mdm2-mediated ubiquitination and enhancing p300-mediated p53 acetylation, linking SOX4 to cell cycle arrest and apoptosis

    Evidence Co-IP, ubiquitination assays, and p53 acetylation assays in cultured cells

    PMID:19234109

    Open questions at the time
    • Physiological tissues where SOX4-p53 axis operates in vivo not defined
    • Whether SOX4-p53 interaction requires the HMG domain specifically was not tested
  2. 2012 High

    Identifying Dicer as a direct SOX4 transcriptional target revealed SOX4's capacity to globally reshape miRNA landscapes, explaining broad downstream effects beyond individual target genes

    Evidence ChIP for promoter binding, siRNA knockdown, miRNA profiling, and rescue with Dicer overexpression in melanoma cells

    PMID:22689055

    Open questions at the time
    • Whether SOX4-Dicer axis operates outside melanoma not established
    • Specific chromatin mechanism of SOX4 at the Dicer promoter not resolved
  3. 2013 High

    Positioning SOX4 as a master regulator of TGF-β-induced EMT through direct transcriptional activation of EZH2, which mediates epigenetic reprogramming via H3K27me3—a pathway later extended by identification of upstream MTA1 and downstream co-repressor complexes

    Evidence ChIP, shRNA, rescue experiments, gene expression profiling, and in vivo xenografts in mammary epithelial and cancer cells

    PMID:23301048 PMID:23764001

    Open questions at the time
    • How SOX4 itself is recruited to the EZH2 promoter and what cofactors are required was unclear
    • Relative contribution of SOX4-EZH2 versus other EMT pathways not quantified
  4. 2013 High

    Demonstrating SOX4 as a direct transcriptional activator of Cald1 during skeletal myoblast differentiation established its role in non-cancer mesenchymal biology

    Evidence EMSA, promoter analysis, siRNA knockdown, and rescue in C2C12 myoblasts

    PMID:24046453

    Open questions at the time
    • In vivo requirement for SOX4 in muscle development not tested with conditional KO
  5. 2015 High

    Revealing that KAT5-mediated acetylation at K95 is essential for SOX4 transcriptional activity, and that HDAC1 antagonizes this modification, established a post-translational toggle controlling SOX4 function

    Evidence In vitro acetylation assay, site-directed K95 mutagenesis, ChIP, and promoter activity assays in C2C12 cells

    PMID:26291311

    Open questions at the time
    • Whether K95 acetylation governs SOX4 activity in EMT or other contexts not tested
    • Other acetylation sites not surveyed
  6. 2015 High

    SOX4 forms a co-repressor complex with EZH2 and HDAC3 at the miR-31 promoter, establishing that SOX4 can recruit both histone methylation and deacetylation machineries for gene silencing, and that miR-31 feeds back to degrade SOX4 mRNA

    Evidence Reciprocal Co-IP, ChIP, methylation analysis, and shRNA knockdown in cancer cell lines

    PMID:25644061

    Open questions at the time
    • Structural basis for SOX4-EZH2-HDAC3 ternary complex not resolved
    • Genome-wide extent of SOX4 co-repressor activity not mapped
  7. 2015 High

    Liver-specific combined deletion of Sox4 and Sox9 revealed cooperative control of bile duct development through co-regulation of TGF-β, Notch, and Hippo-Yap signaling, demonstrating functional redundancy within SoxC family members in organogenesis

    Evidence Single and double conditional KO mice, histology, gene expression analysis

    PMID:26033091

    Open questions at the time
    • Individual direct targets of SOX4 versus SOX9 in bile duct progenitors not dissected
    • Whether SOX4 and SOX9 bind DNA as heterodimers or independently not resolved
  8. 2016 High

    Identifying TMEM2 as a direct SOX4 target sufficient for metastatic colonization and Stxbp6 as a SOX4-regulated modulator of insulin granule exocytosis broadened the functional repertoire of SOX4 from transcription factor to regulator of membrane dynamics in both cancer and endocrine biology

    Evidence ChIP and functional studies in breast cancer cells (TMEM2); single-granule exocytosis measurements and microarray in transgenic β-cells and EndoC-βH2 cells (Stxbp6)

    PMID:26993066 PMID:27328729

    Open questions at the time
    • Whether SOX4-Stxbp6 axis contributes to diabetes in humans not established
    • TMEM2 mechanism of action in metastasis not fully elucidated
  9. 2017 High

    Conditional β-cell SOX4 knockout directly linked SOX4 to Cdkn1a repression and β-cell proliferation, with loss causing progressive diabetes, establishing an essential endocrine function

    Evidence Inducible β-cell-specific KO mice with immunostaining and gene expression analysis

    PMID:28495880

    Open questions at the time
    • Whether SOX4 directly binds the Cdkn1a promoter in β-cells was inferred but not shown by ChIP in that tissue
  10. 2018 High

    Multiple 2018 studies placed SOX4 as a lineage-determination factor in diverse tissues: it controls intestinal tuft/enteroendocrine cell differentiation independently of Atoh1, iNKT cell development via miR-181, and articular cartilage homeostasis via ADAMTS4/5 regulation

    Evidence Intestinal-specific KO plus organoids with epistasis analysis; genetic mouse model with TCR/Ca²⁺ signaling readout; ChIP/luciferase plus organ culture

    PMID:30016600 PMID:30055169 PMID:30287480

    Open questions at the time
    • Whether SOX4 is a pioneer factor in intestinal progenitors (as later shown in liver) not tested
    • How SOX4 cooperates with other SoxC members in these lineages not fully resolved
  11. 2019 High

    Trio-based exome sequencing identified de novo HMG-domain missense variants that abolish DNA binding and transactivation, causally linking SOX4 loss-of-function to a neurodevelopmental syndrome and confirming the HMG domain as essential for all known SOX4 activities

    Evidence In vitro DNA-binding assays, SOX reporter transactivation, and Xenopus knockdown validation of patient-derived variants

    PMID:30661772

    Open questions at the time
    • Full phenotypic spectrum and genotype-phenotype correlations require larger patient cohorts
    • Whether residual partial function exists for specific variants not quantified
  12. 2019 High

    The integrin αvβ6-TGF-β-SOX4 axis was shown to drive immune evasion in triple-negative breast cancer, and epistasis studies placed MTA1 upstream and EZH2 downstream of SOX4 in the TGF-β-EMT cascade, solidifying a linear signaling hierarchy

    Evidence Genetic inactivation plus integrin-blocking antibody in TNBC models; shRNA epistasis across multiple cancer cell lines with TCGA validation

    PMID:31811272 PMID:33005101 PMID:33385331

    Open questions at the time
    • Whether immune evasion is reversible upon SOX4 inhibition in established tumors not tested
    • Direct immunological readouts (T-cell killing assays) not performed
  13. 2020 High

    METTL14-mediated m6A modification of SOX4 mRNA triggers YTHDF2-dependent degradation, identifying epitranscriptomic regulation as a key layer controlling SOX4 protein abundance and its pro-metastatic EMT program

    Evidence MeRIP-seq, RIP, luciferase reporter, METTL14 knockdown/overexpression in colorectal cancer cells

    PMID:32552762

    Open questions at the time
    • Whether m6A regulation of SOX4 operates in non-cancer contexts not established
    • Competition between YTHDF2 and YTHDF3 readers for SOX4 mRNA not resolved
  14. 2020 High

    SOX4 was shown to directly activate CXCL12 and CXCR7 transcription, connecting SOX4 to paracrine regulation of angiogenesis and chemokine signaling in both HCC and breast cancer

    Evidence CRISPR KO, ChIP, luciferase reporter, endothelial chemotaxis/tube formation assays, xenograft models

    PMID:32404985 PMID:33005101

    Open questions at the time
    • Whether SOX4-CXCL12/CXCR7 axes operate in normal tissue homeostasis not tested
  15. 2022 High

    SOX4 coactivates PPARγ by recruiting PRDM16 to form a thermogenic transcriptional complex in beige adipocytes; adipocyte-specific SOX4 deletion causes cold intolerance and obesity, revealing a metabolic function

    Evidence Reciprocal Co-IP, ChIP-qPCR, FAIRE, luciferase reporter, adipocyte-specific conditional KO mice

    PMID:36451857

    Open questions at the time
    • Whether SOX4 acetylation (K95) regulates its interaction with PPARγ/PRDM16 not tested
    • Genome-wide SOX4/PPARγ co-occupancy not mapped
  16. 2024 High

    Direct demonstration that SOX4 acts as a pioneer transcription factor in adult liver: it first closes hepatocyte enhancers (competing with HNF4A) then opens biliary regulatory sequences, mechanistically explaining how SOX4 drives cell fate reprogramming

    Evidence Lineage tracing, chromatin accessibility profiling, ChIP, and temporal SOX4 induction in mouse liver

    PMID:38409161

    Open questions at the time
    • Whether pioneer activity generalizes to other SOX4-dependent lineage switches (intestine, gonad) not tested
    • Structural basis for competitive displacement of HNF4A by SOX4 not resolved
  17. 2024 High

    METTL3-mediated m6A in the SOX4 CDS (distinct from 3'UTR sites) stabilizes SOX4 mRNA via YTHDF3, revealing that different m6A writers and readers can have opposing effects on SOX4 transcript fate depending on modification site

    Evidence MeRIP-seq, RIP, METTL3 knockdown, AAV2-SOX4 overexpression in ovariectomized mice for osteoblast differentiation

    PMID:38195035

    Open questions at the time
    • How CDS versus 3'UTR m6A sites are differentially read by YTHDF2 versus YTHDF3 remains mechanistically unexplained
    • Whether both m6A pathways operate simultaneously in the same cell type not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for SOX4 pioneer activity and HNF4A displacement, the full catalog of genomic loci remodeled by SOX4 across tissues, whether post-translational modifications (acetylation, ubiquitination) regulate pioneer versus co-repressor versus coactivator modes, and the therapeutic targetability of the SOX4-EZH2 axis in cancer
  • No crystal structure of SOX4 HMG domain bound to nucleosomal DNA
  • Genome-wide pioneer factor footprinting in multiple tissues lacking
  • No small-molecule modulators of SOX4 activity reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 16 GO:0003677 DNA binding 11 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 7
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 5 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 3
Partners
EP300EZH2HDAC3KAT5PPARGPRDM16TP53USP20
Complex memberships
SOX4-EZH2-HDAC3 co-repressor complexSOX4-PPARγ-PRDM16 coactivator complexSOX4-p53-p300/CBP complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 SOX4 directly regulates EZH2 expression; EZH2 ablation prevents TGF-β-induced EMT whereas forced EZH2 expression restores EMT in SOX4-deficient cells, establishing SOX4 as an upstream master regulator of EMT through epigenetic reprogramming via EZH2-mediated H3K27me3 ChIP, gene expression profiling, shRNA knockdown, rescue experiments, in vivo xenograft Cancer cell High 23764001
2009 SOX4 interacts with p53 and blocks Mdm2-mediated p53 ubiquitination and degradation; SOX4 also enhances p53 acetylation by interacting with p300/CBP and facilitating p300/CBP/p53 complex formation, promoting cell cycle arrest and apoptosis in a p53-dependent manner Co-immunoprecipitation, ubiquitination assay, p53 acetylation assay, cell cycle/apoptosis assays Proceedings of the National Academy of Sciences of the United States of America High 19234109
2015 SOX4 forms a co-repressor complex with EZH2 and HDAC3 that binds to the miR-31 promoter, repressing miR-31 through H3K27me3 and histone deacetylation; miR-31 in turn targets SOX4 for degradation by binding its 3'-UTR Immunoprecipitation, ChIP, methylation studies, overexpression/shRNA knockdown Molecular cancer High 25644061
2015 SOX4 acetylation at lysine 95 by KAT5 (Tip60) is essential for Cald1 promoter activity during C2C12 myoblast differentiation; KAT5 chromodomain facilitates SOX4 recruitment to the Cald1 promoter and chromatin remodeling; HDAC1 and KAT5 antagonistically switch SOX4 transcriptional activity In vitro acetylation assay, ChIP, promoter activity assay, mutagenesis of lysine 95 Cell death & disease High 26291311
2013 SOX4 directly binds to and activates the caldesmon (Cald1) gene promoter during skeletal myoblast differentiation, as demonstrated by promoter analysis and gel mobility shift assay; CaD overexpression rescues myoblast fusion defects caused by Sox4 silencing Promoter analysis, EMSA (gel mobility shift assay), siRNA knockdown, rescue experiments in C2C12 cells Journal of cell science High 24046453
2019 SOX4 expression is regulated by the integrin αvβ6 receptor, which activates TGFβ from a latent precursor; this integrin αvβ6-TGFβ-SOX4 pathway drives immune evasion in triple-negative breast cancer by suppressing innate and adaptive immune gene expression in tumor cells Genetic inactivation, integrin-blocking monoclonal antibody, gene expression analysis, in vivo TNBC models Cancer cell High 33385331
2016 SOX4 directly binds the TMEM2 promoter and transcriptionally activates TMEM2, which mediates proinvasive and promigratory effects in breast cancer cells; TMEM2 is sufficient to promote metastatic colonization Systematic genomic approach, ChIP, loss-of-function and gain-of-function studies Cancer research High 27328729
2017 SOX4 directly regulates Cdkn1a (p21) expression in pancreatic β-cells; SOX4 knockout induces Cdkn1a, causing a 39% reduction in β-cell proliferation, impaired insulin secretion, and diabetes over time Inducible β-cell-specific knockout mouse, immunostaining, gene expression analysis Diabetes High 28495880
2016 Increased SOX4 expression reduces glucose-induced insulin secretion by upregulating Stxbp6, which causes a fourfold increase in kiss-and-run exocytosis with a fusion pore diameter of ~2 nm insufficient for insulin exit; silencing STXBP6 reverses SOX4-mediated inhibition of hormone release Transgenic mouse model, single-granule exocytosis measurements, microarray, overexpression in EndoC-βH2 cells, siRNA silencing Diabetes High 26993066
2019 In the TGF-β-MTA1-SOX4 signaling axis, MTA1 acts upstream of SOX4, and SOX4 acts upstream of EZH2; both SOX4 and MTA1 are induced by TGF-β and are each required for TGF-β-mediated EMT in multiple cancer cell lines Gene expression profiling screen, shRNA knockdown, epistasis analysis, TCGA pan-cancer validation Oncogene High 31811272
2013 TGF-β rapidly induces SOX4 expression and transcriptional activity in human mammary epithelial cells; SOX4 activation is sufficient to induce N-cadherin, vimentin, and fibronectin expression, and shRNA-mediated SOX4 knockdown significantly delays TGF-β-induced mesenchymal marker expression Conditional activation of Sox4, shRNA knockdown, qPCR, western blot PloS one High 23301048
2018 Sox4 directly binds promoters of ADAMTS4 and ADAMTS5 genes and upregulates their expression in chondrogenic cells, contributing to articular cartilage destruction; adenoviral Sox4 overexpression in mouse femoral head organ culture caused cartilage destruction with increased Adamts5 Luciferase reporter assay, ChIP, adenoviral overexpression, organ culture FASEB journal High 30016600
2018 FHL3 interacts with the Smad2/3 protein complex at the SOX4 promoter, recruits PPM1A phosphatase to Smad2/3, and thereby inhibits SOX4 transcriptional activity and suppresses glioma stem cell self-renewal via downregulation of SOX2 Co-IP, ChIP, in vitro and in vivo tumor sphere formation assays, knockdown Cell death and differentiation High 29955125
2018 SOX4 controls iNKT cell production by inducing MicroRNA-181 (Mir181), which enhances TCR signaling and Ca2+ fluxes in iNKT precursors Genetic mouse model, miRNA expression analysis, TCR signaling and Ca2+ flux measurements The Journal of experimental medicine High 30287480
2012 Sox4 positively regulates Dicer expression by binding to its promoter sequences, and Sox4 knockdown induces a major change in miRNA expression patterns in melanoma cells due to reduced Dicer expression; Dicer overexpression rescues enhanced invasion caused by Sox4 knockdown ChIP (promoter binding), siRNA knockdown, matrigel invasion assay, miRNA expression profiling, rescue experiments Oncogene High 22689055
2020 SOX4 directly binds the CXCL12 promoter (demonstrated by luciferase assay and ChIP) to activate CXCL12 transcription in hepatocellular carcinoma cells; secreted CXCL12 acts on CXCR4 on endothelial cells to modulate chemotaxis, tube formation, and angiogenesis in vivo CRISPR/Cas9 SOX4 knockout, luciferase reporter, ChIP, endothelial chemotaxis and tube formation assays, xenograft Oncogene High 32404985
2019 De novo SOX4 heterozygous missense variants clustering in the HMG DNA-binding domain render SOX4 proteins unable to bind DNA in vitro and unable to transactivate SOX reporter genes in cultured cells, causing a neurodevelopmental syndrome In vitro DNA-binding assay, SOX reporter transactivation assay, trio-based exome sequencing, Xenopus knockdown American journal of human genetics High 30661772
2022 SOX4 functions as a coactivator of PPARγ by binding to PPARγ and recruiting PRDM16, forming a transcriptional complex that elevates thermogenic gene (including Ucp1) expression in beige adipocytes; adipocyte-specific or UCP1+ cell-specific SOX4 deletion causes cold intolerance and obesity Co-IP (endogenous and exogenous), ChIP-qPCR, FAIRE assay, luciferase reporter, adipocyte-specific conditional KO mice Theranostics High 36451857
2024 SOX4 acts as a pioneer transcription factor in vivo: it first binds to and closes hepatocyte regulatory sequences via an overlapping motif with HNF4A, then opens biliary regulatory sequences, thereby initiating hepatobiliary metaplasia and cell fate reprogramming in the adult mouse liver Lineage tracing, chromatin accessibility assay (ATAC-seq equivalent), ChIP, in vivo SOX4 induction in mouse liver Nature communications High 38409161
2015 SOX4 and SOX9 cooperatively control bile duct development; liver-specific combined inactivation reveals that both factors co-regulate TGF-β, Notch, and Hippo-Yap signaling mediators, control formation of primary cilia, and stimulate secretion of laminin α5 Liver-specific conditional KO (single and double), histology, gene expression analysis Developmental biology High 26033091
2017 SOX4 represses transcription of the sex-determining gene Sox9 via an upstream testis-specific enhancer core (TESCO) element in fetal gonads; Sox4 deficiency increases testis cord number and reduces male germ cell differentiation markers (Nanos2, Dnmt3l) while elevating pluripotency genes (Cripto, Nanog) Sox4-deficient mouse model, luciferase reporter for TESCO, immunostaining, gene expression analysis Developmental biology High 28118982
2018 Sox4 is required for tuft and enteroendocrine cell differentiation in the intestine independently of Atoh1; Sox4 overexpression is sufficient to induce tuft and enteroendocrine cell differentiation even in Atoh1-null organoids, placing Sox4 in a parallel secretory differentiation pathway Intestinal epithelial-specific Sox4 conditional KO mice, organoids, single-cell RNA-seq, helminth infection model, Sox4-inducible Atoh1-KO organoids Gastroenterology High 30055169
2015 miR-132 directly targets SOX4 3'UTR to suppress its expression; loss of miR-132 leads to elevated SOX4 and promotes lung cancer cell migration and invasion; SOX4 re-introduction reverses the anti-invasion effects of miR-132 Luciferase reporter assay, western blot, migration/invasion assays, xenograft Journal of thoracic disease Medium 26543603
2020 METTL14-mediated m6A modification of SOX4 mRNA promotes its degradation via a YTHDF2-dependent pathway; METTL14 knockdown abolishes SOX4 mRNA m6A modification and elevates SOX4 expression, promoting colorectal cancer metastasis through SOX4-mediated EMT MeRIP-seq, RNA-seq, RIP, luciferase reporter, METTL14 knockdown/overexpression Molecular cancer High 32552762
2024 METTL3-mediated m6A modification of SOX4 mRNA in its coding sequence (CDS) region enhances SOX4 mRNA stability; YTHDF3 is the m6A reader that modulates SOX4 mRNA and protein levels; this METTL3-m6A-SOX4-YTHDF3 axis regulates osteoblast proliferation and differentiation MeRIP-seq, RNA-seq, RIP assay, METTL3 knockdown, AAV2-mediated SOX4 overexpression in OVX mice Cellular signalling High 38195035
2020 TGF-β-downstream transcription factor SOX4 is selectively upregulated in CD39+ Tregs; SOX4 overexpression strongly increases CD39 expression while CRISPR/Cas9 knockout of SOX4 in Tregs decreases CD39 expression, establishing SOX4 as a regulator of CD39-mediated immune regulation SOX4 overexpression, CRISPR/Cas9 KO in primary human Tregs, flow cytometry FASEB journal High 32319705
2019 CASC15 lncRNA enhances YY1 transcription factor-mediated regulation of the SOX4 promoter; CASC15 is chromosomally adjacent to SOX4 and regulates its expression, controlling leukemia cell survival and proliferation ChIP, luciferase reporter, CASC15 knockdown/overexpression, colony formation assay Molecular cancer Medium 28724437
2015 Estrogen (E2) upregulates SOX4 expression in prostate cancer through formation of a protein complex between ERβ and AR; both ERβ and AR bind to the SOX4 promoter in response to E2 as confirmed by ChIP; DHT/AR represses SOX4 transcription Co-immunoprecipitation, ChIP, luciferase reporter assay, siRNA knockdown The Prostate High 26015225
2022 USP20 deubiquitinase interacts with SOX4 (confirmed by Co-IP) and stabilizes SOX4 protein by preventing its ubiquitination-mediated degradation, thereby promoting colorectal cancer EMT and metastasis Co-IP, western blot, ubiquitination assay, CCK-8, transwell, rescue assay Pathology, research and practice Medium 35405623
2020 SOX4 directly binds to the CXCR7 promoter (by ChIP and luciferase assay) to upregulate CXCR7 transcription in breast cancer cells, and the SOX4/CXCR7 axis mediates cell migration and invasion; CXCR7 inhibitor CCX771 reverses SOX4-driven migration ChIP, dual-luciferase reporter assay, lentiviral OE/KD, transwell assay, bioluminescent in vivo imaging Cancer cell international High 33005101
2024 SOX4 drives NSCLC progression by enhancing transcription of BMI1; BMI1 then promotes H2A ubiquitination (H2Aub), which suppresses ZNF24 expression, leading to increased VEGF-A secretion and angiogenesis In vitro and in vivo OE/KD experiments, ChIP (SOX4 binding to BMI1 promoter implied), orthotopic mouse models Cell death & disease Medium 39349443
2014 Sox4 directly binds to the Cyr61 promoter and transcriptionally upregulates Cyr61 expression in colon cancer cells; overexpression increases and siRNA knockdown reduces Cyr61 expression Luciferase reporter assay, ChIP, siRNA knockdown, PCR-based microarray Cellular physiology and biochemistry Medium 25059387
2019 SOX11 and SOX4 dictate embryonic epidermal state and regulate genes involved in cytoskeletal/ECM organization; FSCN1 (fascin) is identified as a critical direct transcriptional target of SOX11 and SOX4 regulating cell migration during wound repair Wound-edge mouse model, Sox11/Sox4 double-deficient mice, gene expression analysis, functional migration/re-epithelialization assays Nature communications High 31492871
2021 SOX4 transcriptionally activates LINC00511; LINC00511 in turn sponges miR-195-5p to elevate SOX4 expression, forming a positive feedback loop that also recruits EZH2 to the PTEN promoter to epigenetically repress PTEN and activate PI3K/AKT in gastric cancer ChIP, luciferase reporter, RIP, RNA-seq, siRNA knockdown Journal of cellular and molecular medicine Medium 34427967
2015 Sox4 participates in regulation of Schwann cell myelination; transgenic Sox4 overexpression in Schwann cells causes temporary delay in PNS myelination and aggravates neuropathic phenotype in a CMT4C mouse model; Sox4 protein expression is post-transcriptionally regulated in Schwann cells Transgenic mouse overexpression in Schwann cells, crossing with CMT4C model, histological analysis The European journal of neuroscience Medium 25899854
2023 SOX4 is aberrantly activated in myofibroblast-like cancer-associated fibroblasts (myCAFs) in pancreatic cancer and promotes secretion of MMP11, which induces early cancer cell invasion Single-cell RNA sequencing, CAF differentiation trajectory analysis, functional invasion assays Biochimica et biophysica acta. Molecular basis of disease Medium 37633471
2019 circ-DONSON is localized in the nucleus and recruits the NURF chromatin-remodeling complex (containing SNF2L, BPTF, RBBP4) to the SOX4 promoter to initiate SOX4 transcription in gastric cancer Mass spectrometry, RIP, RNA pulldown, EMSA, ChIP, DNA-FISH, DNA accessibility assay Molecular cancer High 30922402
2022 SOX4 promotes WNT2 transcription in gastric cancer stem cells (GCSCs); WNT2 in turn activates canonical WNT2/FZD8/β-catenin signaling that upregulates SOX4, forming a positive feedback loop maintaining GCSC self-renewal ChIP, luciferase reporter, WNT2-blocking monoclonal antibody, GCSC xenograft model Oncogene High 37634009

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. Cancer cell 419 23764001
2020 METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer. Molecular cancer 324 32552762
2012 SOX4 induces epithelial-mesenchymal transition and contributes to breast cancer progression. Cancer research 232 22787120
2019 Circular RNA circ-DONSON facilitates gastric cancer growth and invasion via NURF complex dependent activation of transcription factor SOX4. Molecular cancer 203 30922402
2020 Integrin αvβ6-TGFβ-SOX4 Pathway Drives Immune Evasion in Triple-Negative Breast Cancer. Cancer cell 179 33385331
2012 The role of SRY-related HMG box transcription factor 4 (SOX4) in tumorigenesis and metastasis: friend or foe? Oncogene 175 23246969
2019 SOX4: The unappreciated oncogene. Seminars in cancer biology 169 31445218
2000 Roles of Sox4 in central nervous system development. Brain research. Molecular brain research 164 10925158
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 111 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
2015 Transcription factors SOX4 and SOX9 cooperatively control development of bile ducts. Developmental biology 96 26033091
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 87 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 82 30055169
2019 A TGF-β-MTA1-SOX4-EZH2 signaling axis drives epithelial-mesenchymal transition in tumor metastasis. Oncogene 78 31811272
2006 Knockdown of Sox4 expression by RNAi induces apoptosis in ACC3 cells. Oncogene 78 16636670
2016 MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1. Oncotarget 76 27119506
2016 MicroRNA-338-3p suppresses metastasis of lung cancer cells by targeting the EMT regulator Sox4. American journal of cancer research 74 27186391
2019 SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair. Nature communications 73 31492871
2013 miR-129-2 suppresses proliferation and migration of esophageal carcinoma cells through downregulation of SOX4 expression. International journal of molecular medicine 68 23677061
2016 TMEM2 Is a SOX4-Regulated Gene That Mediates Metastatic Migration and Invasion in Breast Cancer. Cancer research 67 27328729
2012 Sox4-mediated Dicer expression is critical for suppression of melanoma cell invasion. Oncogene 61 22689055
2015 The microRNA-212/132 cluster regulates B cell development by targeting Sox4. The Journal of experimental medicine 60 26371188
2019 LINC01133 inhibits breast cancer invasion and metastasis by negatively regulating SOX4 expression through EZH2. Journal of cellular and molecular medicine 58 31557401
2015 SOX4 contributes to the progression of cervical cancer and the resistance to the chemotherapeutic drug through ABCG2. Cell death & disease 55 26583330
2020 SOX4 activates CXCL12 in hepatocellular carcinoma cells to modulate endothelial cell migration and angiogenesis in vivo. Oncogene 54 32404985
1993 Characterization and mapping of the human SOX4 gene. Mammalian genome : official journal of the International Mammalian Genome Society 53 8268656
2016 Increased Expression of the Diabetes Gene SOX4 Reduces Insulin Secretion by Impaired Fusion Pore Expansion. Diabetes 52 26993066
2017 P53-miR-191-SOX4 regulatory loop affects apoptosis in breast cancer. RNA (New York, N.Y.) 50 28450532
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 48 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
2024 The SOX4/EZH2/SLC7A11 signaling axis mediates ferroptosis in calcium oxalate crystal deposition-induced kidney injury. Journal of translational medicine 46 38169402
2015 miR-132 inhibits lung cancer cell migration and invasion by targeting SOX4. Journal of thoracic disease 46 26543603
2019 De Novo SOX4 Variants Cause a Neurodevelopmental Disease Associated with Mild Dysmorphism. American journal of human genetics 45 30661772
2020 SOX4 promotes the growth and metastasis of breast cancer. Cancer cell international 44 33005101
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 43 32319705
2022 SOX4 is a novel phenotypic regulator of endothelial cells in atherosclerosis revealed by single-cell analysis. Journal of advanced research 42 36585108
2017 Amplification of SOX4 promotes PI3K/Akt signaling in human breast cancer. Breast cancer research and treatment 42 28176176
2015 MiR-211 inhibits cell proliferation and invasion of gastric cancer by down-regulating SOX4. International journal of clinical and experimental pathology 41 26823713
2020 NORAD accelerates chemo-resistance of non-small-cell lung cancer via targeting at miR-129-1-3p/SOX4 axis. Bioscience reports 39 31894841
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 promotes beige adipocyte-mediated adaptive thermogenesis by facilitating PRDM16-PPARγ complex. Theranostics 35 36451857
2019 miR-140-5p is negatively correlated with proliferation, invasion, and tumorigenesis in malignant melanoma by targeting SOX4 via the Wnt/β-catenin and NF-κB cascades. Journal of cellular physiology 35 31385607
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
2020 lncRNA XIST promotes glioma proliferation and metastasis through miR-133a/SOX4. Experimental and therapeutic medicine 34 32104215
2018 miR-363-3p Inhibits Osteosarcoma Cell Proliferation and Invasion via Targeting SOX4. Oncology research 33 29471893
2017 SOX4 regulates gonad morphogenesis and promotes male germ cell differentiation in mice. Developmental biology 33 28118982
2018 SOX4 controls invariant NKT cell differentiation by tuning TCR signaling. The Journal of experimental medicine 32 30287480
2023 WNT2-SOX4 positive feedback loop promotes chemoresistance and tumorigenesis by inducing stem-cell like properties in gastric cancer. Oncogene 31 37634009
2020 LncRNA JPX promotes cervical cancer progression by modulating miR-25-3p/SOX4 axis. Cancer cell international 31 32943989
2016 MicroRNA-140 Inhibits Cell Proliferation in Gastric Cancer Cell Line HGC-27 by Suppressing SOX4. Medical science monitor : international medical journal of experimental and clinical research 31 27353653
2015 Upregulated Expression of SOX4 Is Associated with Tumor Growth and Metastasis in Nasopharyngeal Carcinoma. Disease markers 31 26578818
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.) 30 35800365
2018 Stem-Like Signature Predicting Disease Progression in Early Stage Bladder Cancer. The Role of E2F3 and SOX4. Biomedicines 30 30072631
2018 Dysregulation of KCNQ1OT1 promotes cholangiocarcinoma progression via miR-140-5p/SOX4 axis. Archives of biochemistry and biophysics 30 30243712
2015 MicroRNA-204 inhibits cell proliferation in T-cell acute lymphoblastic leukemia by down-regulating SOX4. International journal of clinical and experimental pathology 30 26464665
2020 Circular RNA UBAP2 contributes to tumor growth and metastasis of cervical cancer via modulating miR-361-3p/SOX4 axis. Cancer cell international 28 32760224
2019 LncRNA FENDRR attenuates colon cancer progression by repression of SOX4 protein. OncoTargets and therapy 27 31213846
2019 MicroRNA-130a modulates a radiosensitivity of rectal cancer by targeting SOX4. Neoplasia (New York, N.Y.) 27 31387015
2017 MicroRNA-138 attenuates epithelial-to-mesenchymal transition by targeting SOX4 in clear cell renal cell carcinoma. American journal of translational research 27 28861152
2018 FHL3 links cell growth and self-renewal by modulating SOX4 in glioma. Cell death and differentiation 26 29955125
2015 KAT5-mediated SOX4 acetylation orchestrates chromatin remodeling during myoblast differentiation. Cell death & disease 26 26291311
2021 LINC00511 promotes gastric cancer progression by regulating SOX4 and epigenetically repressing PTEN to activate PI3K/AKT pathway. Journal of cellular and molecular medicine 25 34427967
2020 miR-30a inhibits androgen-independent growth of prostate cancer via targeting MYBL2, FOXD1, and SOX4. The Prostate 25 32294305
2017 SOX4 Allows Facultative β-Cell Proliferation Through Repression of Cdkn1a. Diabetes 25 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
2021 THAP9-AS1/miR-133b/SOX4 positive feedback loop facilitates the progression of esophageal squamous cell carcinoma. Cell death & disease 23 33854048
2021 ROS/TGF-β signal mediated accumulation of SOX4 in OA-FLS promotes cell senescence. Experimental gerontology 23 34742854
2024 Cellular reprogramming in vivo initiated by SOX4 pioneer factor activity. Nature communications 22 38409161
2020 LncRNA SNHG5 regulates SOX4 expression through competitive binding to miR-489-3p in acute myeloid leukemia. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 22 32266420
2020 Anillin facilitates cell proliferation and induces tumor growth of hepatocellular carcinoma via miR-138/SOX4 axis regulation. Translational oncology 21 32645689
2020 MYC-activated lncRNA HNF1A-AS1 overexpression facilitates glioma progression via cooperating with miR-32-5p/SOX4 axis. Cancer medicine 21 33448691
2013 Expression of Sox4 and Sox11 is regulated by multiple mechanisms during retinal development. FEBS letters 21 23313252
2024 METTL3-mediated m6A modification of SOX4 regulates osteoblast proliferation and differentiation via YTHDF3 recognition. Cellular signalling 20 38195035
2024 SOX4-BMI1 axis promotes non-small cell lung cancer progression and facilitates angiogenesis by suppressing ZNF24. Cell death & disease 20 39349443
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
2024 ALKBH5-mediated m6A modification of circFOXP1 promotes gastric cancer progression by regulating SOX4 expression and sponging miR-338-3p. Communications biology 19 38745044
2021 LncRNA SNHG5 promotes cervical cancer progression by regulating the miR-132/SOX4 pathway. Autoimmunity 19 33622094
2013 Sox4-mediated caldesmon expression facilitates differentiation of skeletal myoblasts. Journal of cell science 19 24046453
2023 The ALKBH5/SOX4 axis promotes liver cancer stem cell properties via activating the SHH signaling pathway. Journal of cancer research and clinical oncology 18 37646828
2021 miRNA-214-5p inhibits prostate cancer cell proliferation by targeting SOX4. World journal of surgical oncology 18 34863188
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
2020 LINC01305 inhibits malignant progression of cervical cancer via miR-129-5p/Sox4 axis. American journal of translational research 17 33312390
2022 E2F7 enhances hepatocellular carcinoma growth by preserving the SP1/SOX4/Anillin axis via repressing miRNA-383-5p transcription. Molecular carcinogenesis 16 35924788
2021 MiR-129-5p Promotes Radio-sensitivity of NSCLC Cells by Targeting SOX4 and RUNX1. Current cancer drug targets 16 33858314
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
2021 Propofol Suppresses Gastric Cancer Progression by Regulating circPDSS1/miR-1324/SOX4 Axis. Cancer management and research 14 34377022
2017 MicroRNA-25 suppresses proliferation, migration, and invasion of osteosarcoma by targeting SOX4. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 14 28705117
2023 circGRAMD1B contributes to migration, invasion and epithelial-mesenchymal transition of lung adenocarcinoma cells via modulating the expression of SOX4. Functional & integrative genomics 13 36867268
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
2022 USP20 regulates the stability of EMT transcription factor SOX4 and influences colorectal cancer metastasis. Pathology, research and practice 13 35405623
2015 Sox4 participates in the modulation of Schwann cell myelination. The European journal of neuroscience 13 25899854
2021 MiR-296-3p inhibits cell proliferation by the SOX4-Wnt/βcatenin pathway in triple-negative breast cancer. Journal of biosciences 12 34785625