Affinage

ETV4

ETS translocation variant 4 · UniProt P43268

Length
484 aa
Mass
53.9 kDa
Annotated
2026-06-09
100 papers in source corpus 52 papers cited in narrative 52 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ETV4 (PEA3/E1AF) is an ETS-family transcription factor that integrates receptor tyrosine kinase signaling into a transcriptional program driving tumor cell invasion, metastasis, proliferation, and immune modulation across diverse tissues (PMID:1923525, PMID:8570199, PMID:23918374). Its DNA-binding activity is intrinsically autoinhibited by two independent elements flanking the ETS domain: a C-terminal α-helix that perturbs the DNA-recognition helix and an intrinsically disordered N-terminal inhibitory domain whose lysine acetylation relieves repression; an additional redox switch, in which disulfide-linked dimerization lowers DNA-binding affinity 40–200-fold, further tunes activity (PMID:25866208, PMID:28161714). ETV4 is activated downstream of HER2/Neu, HGF/c-Met, FGFR, and Ret through Ras-dependent ERK and JNK/SAPK MAPK pathways (PMID:9467955, PMID:10836994, PMID:19898483, PMID:33983905), and ERK phosphorylation at Ser73 stabilizes the protein by blocking COP1-mediated ubiquitination (PMID:28373072). Activated ETV4 recruits the Mediator subunit MED25 through multivalent contacts that relieve its own autoinhibition, co-occupying enhancers and jointly driving target-gene transcription (PMID:28728983). Its target program prominently includes matrix metalloproteinases (MMP-1, -3, -9, -13, MT1-MMP) and the uPA/uPAR and Rho/ROCK invasion machinery (PMID:7731700, PMID:10208438, PMID:16322223, PMID:29996935, PMID:30914208), cell-cycle regulators (Cyclin D1, Cyclin D3, and repression of CDKN1A/p21 with reduced p53) (PMID:17467662, PMID:29117940, PMID:32791988), and immune/chemokine effectors (PD-L1, CCL2, CXCL1/8, TNF-α) that reshape the tumor microenvironment (PMID:35296440, PMID:36907560, PMID:37670477). ETV4 also acts as a transcriptional cofactor: it forms complexes with HIF-1/2α to co-activate hypoxia-inducible genes, with the estrogen receptor to license its genomic binding and chromatin accessibility, and with YAP to potentiate Hippo-pathway transcription (PMID:22075993, PMID:32046982, PMID:35296440). Beyond oncogenesis, ETV4 functions redundantly with ETV5 in GDNF/Ret-driven ureteric bud branching and renal development, in motor and sensory neuron targeting, and in embryonic stem cell self-renewal (PMID:12372283, PMID:19898483, PMID:24089499, PMID:26224636, PMID:26894589).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1991 High

    Established that ETV4 is a sequence-specific enhancer-binding factor with direct functional output, by showing it binds a defined element in the uPA promoter required for enhancer activity.

    Evidence DNase I footprinting, EMSA, and mutant reporter constructs on the uPA promoter

    PMID:1923525

    Open questions at the time
    • Did not address upstream signals controlling ETV4
    • No genome-wide binding landscape
  2. 1996 High

    Linked ETV4 transcriptional activity to a tumor-relevant phenotype by showing forced expression confers invasion via MMP induction, defining its proteolytic invasion program.

    Evidence Stable E1AF transfection of MCF-7 cells with in vitro/in vivo invasion assays and MMP-1/3/9 reporter assays

    PMID:7731700 PMID:8570199

    Open questions at the time
    • Direct vs indirect promoter binding not fully resolved for all MMPs
    • Did not address endogenous requirement
  3. 1997 High

    Placed ETV4 downstream of an oncogenic RTK by showing HER2/Neu activates it through dual Ras-dependent ERK and JNK pathways, and that ETV4 was required for invasion.

    Evidence Dominant-negative pathway-mutant reporter assays; antisense knockdown with invasion readouts

    PMID:9176403 PMID:9380403 PMID:9467955

    Open questions at the time
    • Phosphosite targets within ETV4 not mapped at this stage
    • Autoregulatory loop based on reporter/EMSA only
  4. 2000 High

    Defined the domain architecture of ETV4, revealing a strong activation domain flanked by independent inhibitory regions and intrinsic autoinhibition of DNA binding.

    Evidence Deletion mutagenesis with transactivation reporters and antibody-relieved EMSA in COS cells

    PMID:11096072

    Open questions at the time
    • Structural basis of autoinhibition unresolved
    • Did not identify partners that relieve autoinhibition
  5. 2002 High

    Demonstrated a developmental, non-oncogenic role by showing ETV4 coordinates motor neuron central positioning and terminal axon branching.

    Evidence Pea3 knockout mouse neuroanatomy and muscle innervation analysis

    PMID:12372283

    Open questions at the time
    • Downstream transcriptional targets in neurons not defined here
    • Redundancy with ETV5 not addressed
  6. 2009 High

    Established ETV4/ETV5 as essential, dose-dependent effectors of GDNF/Ret signaling in kidney branching, identifying direct developmental target genes.

    Evidence Compound Etv4/Etv5 knockout mice with renal histology and target gene (Cxcr4, Met, Mmp14) analysis

    PMID:19898483 PMID:26894589

    Open questions at the time
    • Direct promoter occupancy of renal targets not shown
    • Mechanism distinguishing migration from proliferation refined later
  7. 2011 High

    Revealed ETV4 acts as a transcriptional cofactor beyond direct DNA binding by forming a complex with HIF-1/2α to co-activate a subset of hypoxia-inducible genes.

    Evidence Mammalian two-hybrid, FRET, domain mapping, ChIP at PHD2 promoter, genome-wide expression profiling

    PMID:22075993

    Open questions at the time
    • Stoichiometry/structure of ETV4-HIF complex unresolved
    • Scope limited to ~7.7% of hypoxic transcripts
  8. 2015 High

    Provided the structural mechanism of ETV4 DNA recognition and uncovered a redox-dependent regulatory switch via disulfide-linked dimerization.

    Evidence X-ray crystallography of ETS domain alone and DNA-bound, plus disulfide reduction and affinity measurements

    PMID:25866208

    Open questions at the time
    • In vivo relevance of disulfide dimerization not established
    • Full-length protein not crystallized
  9. 2017 High

    Resolved the molecular basis of autoinhibition and its regulation, showing a C-terminal helix and a disordered acetylation-regulated N-terminal domain restrain DNA binding, and that MED25 relieves autoinhibition through multivalent contacts.

    Evidence Crystal structures, NMR, acetylation assays; NMR/ITC/SPR mapping plus ChIP-seq and knockdown for MED25

    PMID:28161714 PMID:28728983

    Open questions at the time
    • Acetyltransferase responsible for NID acetylation not identified
    • In vivo MED25 dependency across contexts not fully mapped
  10. 2017 Medium

    Identified post-translational stabilization of ETV4, showing ERK phosphorylation at Ser73 blocks COP1-mediated ubiquitination and degradation.

    Evidence Ser73 mutagenesis, ETV4-COP1 Co-IP, ubiquitination assays under ERK modulation

    PMID:28373072

    Open questions at the time
    • Single Co-IP for COP1 interaction without reciprocal validation in vivo
    • Quantitative contribution to steady-state ETV4 unclear
  11. 2013 High

    Demonstrated ETV4 selectively drives metastasis rather than primary tumor growth downstream of PI3K/Ras in prostate cancer.

    Evidence Pten-loss/Kras mouse model with lineage tracing and Etv4 shRNA knockdown in metastasis assays

    PMID:23918374

    Open questions at the time
    • Metastasis-specific target genes not fully defined here
    • Mechanism separating growth from dissemination unresolved
  12. 2020 High

    Showed ETV4 is a licensing cofactor for estrogen receptor genomic binding, chromatin accessibility, and nuclear translocation, broadening its role to nuclear-receptor cooperativity.

    Evidence CRISPR ETV4 deletion with ER ChIP-seq, RNA-seq, ATAC-seq, and estrogen-dependent growth assays

    PMID:32046982

    Open questions at the time
    • Direct ETV4-ER physical interaction not biochemically mapped
    • Pioneer vs cooperative role not distinguished
  13. 2022 Medium

    Extended ETV4's cofactor activity to the Hippo pathway and immune evasion by showing it binds YAP to augment YAP/TEAD4 transcription and induce myeloid-recruiting chemokines.

    Evidence Co-IP, nuclear fractionation, YAP/TEAD4 reporter, ChIP, in vivo immune phenotyping in HCC

    PMID:35296440 PMID:36907560 PMID:37670477

    Open questions at the time
    • ETV4-YAP interaction surface not structurally defined
    • Co-IP-based interaction without reciprocal in vivo validation
  14. 2023 Medium

    Connected ETV4 to metabolic control by showing it drives HK1-dependent glycolysis/lactate to activate mTORC1, with an HDAC6-G3BP2 stress response engaged upon ETV4 loss.

    Evidence ETV4 knockdown, HK1 reporter, lactate/mTORC1 measurements, HDAC6-G3BP2 Co-IP, TSC2 deacetylation and lysosomal fractionation in NSCLC

    PMID:36823378

    Open questions at the time
    • Single-lab pathway with Co-IP-based complexes
    • Direct ETV4 occupancy at HK1 not as deeply mapped as transcriptional output
  15. 2024 Medium

    Established ETV4 as a mediator of transcriptional plasticity and therapy resistance by showing it occupies IKZF1-bound enhancers to sustain MYC after IMiD-induced IKZF1 loss.

    Evidence ETV4 and IKZF1 ChIP-seq, CRISPR ETV4 deletion, viability assays in IMiD-resistant myeloma

    PMID:37934799

    Open questions at the time
    • Mechanism of ETV4 recruitment to vacated enhancers unclear
    • Generality across other resistance settings untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct ETV4 regulatory layers — autoinhibition relief, acetylation, redox dimerization, MED25 multivalency, and cofactor partnerships (HIF, ER, YAP, IKZF1) — are integrated to select context-specific target programs remains unresolved.
  • No unified model linking PTM state to partner choice
  • Endogenous ETV4 vs ETV1/ETV5 division of labor across tissues incompletely defined
  • Structure of full-length ETV4 in cofactor complexes lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1474244 Extracellular matrix organization 3
Partners
COP1ESR1HIF1AIKZF1MED25SP1TEAD4YAP1

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 PEA3 (ETV4) binds to a specific enhancer element (PEA3 binding site juxtaposed to an AP-1 site) in the human urokinase-type plasminogen activator (uPA) gene promoter and is required for enhancer activity, as demonstrated by footprinting, gel retardation, and transient transfection with deletion/point mutations. DNase I footprinting, gel retardation (EMSA), transient transfection with deletion and point-mutant reporter constructs Oncogene High 1923525
1995 E1AF (ETV4) transcriptionally activates three different subclasses of matrix metalloproteinase (MMP) gene promoters (stromelysin/MMP-3, type I collagenase/MMP-1, and 92 kDa type IV collagenase/MMP-9), increasing CAT reporter activity ~10–20-fold in transient expression assays. Transient co-transfection reporter (CAT) assays with MMP promoter constructs Oncogene Medium 7731700
1996 Transfection of E1AF (ETV4) expression plasmid into non-invasive MCF-7 breast cancer cells confers invasive and motile activities accompanied by increased MMP-9 expression, establishing a direct functional link between E1AF and tumor cell invasion. Stable transfection of E1AF expression vector into MCF-7 cells, in vitro invasion assay, in vivo tumor implantation, Northern blot for MMP-9 Oncogene High 8570199
1996 PEA3 (ETV4) transactivates the vimentin gene promoter through a PEA3 binding site, as shown by transient transfection assays in mammary epithelial and tumor cell lines. Transient transfection reporter assay with vimentin promoter constructs in multiple cell lines Oncogene Medium 8895512
1997 E1AF (ETV4) activates the human p21(Waf1/Cip1) promoter by interacting with Ets-binding sites near p53-responsive elements, in a p53-independent manner, as demonstrated by deletion of EBS abolishing activity in p53-null cells. Transient transfection reporter assay with p21 promoter constructs (wild-type and EBS deletion mutants) in SiHa and Saos2 cells; Northern blot showing correlation of p21 and E1AF under cisplatin treatment Biochemical and biophysical research communications Medium 9223430
1997 Antisense E1AF (ETV4) transfection in HSC3 oral squamous cell carcinoma cells reduces MMP-1, -3, and -9 expression and decreases invasive potential both in vitro and in vivo, establishing a required role of E1AF in MMP-driven invasion. Antisense expression vector transfection, mRNA/protein quantification, in vitro 3D raft invasion culture, in vivo nude mouse implantation The American journal of pathology High 9176403
1997 PEA3 (ETV4) is a downstream target of the HER2/Neu receptor tyrosine kinase; HER2/Neu upregulates PEA3 transcriptional activity through two Ras-dependent MAPK pathways (ERK and SAPK/JNK), as demonstrated using dominant-negative signaling mutants. Co-transfection reporter assay with constitutively active HER2/Neu and dominant-negative Ras (Rap1a), ERK pathway mutants, and JNK pathway mutants; ERK/JNK kinase activation assays Oncogene High 9467955
1997 HER2/Neu overexpression initiates a signaling cascade that increases PEA3 (ETV4) transcriptional activity; transcriptionally activated PEA3 stimulates both HER2/neu and PEA3 gene transcription by binding to sites in their promoters, forming an autoregulatory loop. Reporter assay, EMSA/DNA-binding to HER2 and PEA3 promoters, co-transfection experiments in breast cancer cells Oncogene Medium 9380403
1999 E1AF (ETV4) overexpression in fibrosarcoma cells induces MT1-MMP expression, activates secreted pro-MMP-2, and increases cell motility and invasion, contributing to metastatic capacity in vivo. Stable transfection of E1AF cDNA into QR-32 fibrosarcoma cells, MMP-2/MT1-MMP expression analysis, in vitro motility/invasion assays, in vivo pulmonary metastasis assay Oncogene Medium 10208438
2000 PEA3 (ETV4) contains multiple functional domains: a strong N-terminal activation domain flanked by two inhibitory regions that independently suppress activity, and the ETS domain plus flanking regions that independently inhibit DNA binding in mammalian cells; antibody relief of autoinhibition was required to detect DNA binding in vitro. Deletion mutagenesis in COS cells with reporter assays (transactivation domain mapping); EMSA with PEA3 deletion mutants and PEA3-specific antibody The Journal of biological chemistry High 11096072
2000 HGF upregulates E1AF (ETV4) expression, which in turn activates MMP-1, -3, and -9 promoters through Ets-binding sites, driving oral cancer cell invasion; antisense E1AF blocks HGF-induced MMP upregulation and invasion. HGF treatment of HSC3 cells, RT-PCR for E1AF/MMP mRNAs, CAT reporter assays with wild-type and Ets-site-mutant MMP-9 promoters, organotypic raft invasion culture Carcinogenesis High 10836994
2001 PEA3 (ETV4) is upregulated in response to Wnt1 expression in mammary epithelial cells and potently activates COX-2 transcription; the NF-IL6 site in the COX-2 promoter is important for PEA3 responsiveness, as shown by promoter mapping. Transient transfection reporter assay with COX-2 promoter deletion constructs in Wnt1-expressing cells; Western blot for PEA3 in Wnt1 cells The Journal of biological chemistry Medium 11274170
2001 Each member of the pea3 subfamily (pea3/ETV4, er81/ETV1, erm/ETV5) is coordinately overexpressed in MMTV-neu mammary tumors; expression of a dominant-negative pea3 transgene in MMTV-neu mice dramatically delayed mammary tumor onset and reduced tumor number/size, establishing a required role for PEA3 factors in HER2/Neu-mediated oncogenesis. Transgenic mouse model (MMTV-neu × MMTV-dominant-negative-pea3 bitransgenic), tumor latency/incidence monitoring, RT-PCR for transgene expression in tumors Current biology : CB High 11719215
2002 In Pea3 (ETV4) mutant mice, specific motor neuron pools fail to arborize normally within target muscles and are mispositioned within the spinal cord, establishing that peripherally-induced ETS gene expression coordinates central positioning and terminal branching of spinal motor neurons. Pea3 knockout mouse analysis, histological examination of muscle innervation, spinal cord neuroanatomy Neuron High 12372283
2004 PEA3 (ETV4) cooperates with beta-catenin/Lef-1 and c-Jun to activate osteopontin (OPN) transcription; co-transfection of all four factors increased luciferase expression ~280-fold and induced endogenous OPN in a rat mammary cell line. Transient transfection reporter assay with OPN promoter-luciferase, co-transfection of beta-catenin, Lef-1, PEA3, and c-Jun in various combinations; endogenous OPN induction by RT-PCR The Journal of biological chemistry Medium 14990565
2004 E1AF (ETV4) binds to and activates the β1,4-galactosyltransferase I (GalT I) promoter through an Ets-binding site at -205 to -200; stable transfection of E1AF in low-metastatic cells increased GalT I expression and cell migration. Deletion and mutation analysis of GalT I promoter-luciferase reporter, EMSA with anti-E1AF antibody, stable transfection and migration assays The Journal of biological chemistry Medium 15611127
2005 E1AF (ETV4) activates the Rho/Rho-associated kinase (ROCK) pathway in NSCLC cells: E1AF-transfected cells have increased GTP-bound Rho and higher myosin light chain phosphorylation (a ROCK effector), and ROCK inhibitor Y27632 suppresses E1AF-induced motility, invasion, and tumorigenesis. Rho activation assay (GTP-bound Rho pull-down), MLC phosphorylation Western blot, ROCK inhibitor treatment, in vitro motility/invasion assays, in vivo nude mouse tumor/metastasis assay Cancer research High 16322223
2007 E1AF (ETV4) forms a protein complex with Sp1, contributes to Sp1 phosphorylation, and functions as a mediator between EGF signaling and Sp1 transcriptional activity; Sp1 brings E1AF to the GalT V promoter to activate its transcription and promote glioma invasion. Co-immunoprecipitation (E1AF-Sp1 complex), Sp1 phosphorylation Western blot, ChIP assay on GalT V promoter, reporter assay, invasion assay in glioma cells Molecular and cellular biology Medium 17938207
2007 E1AF (ETV4) promotes breast cancer cell cycle progression by directly upregulating Cyclin D3 transcription; E1AF RNAi reduces Cyclin D3 expression and cell cycle progression, and forced Cyclin D3 expression rescues the E1AF knockdown phenotype. Luciferase reporter assay for Cyclin D3 promoter activity, siRNA knockdown, rescue by Cyclin D3 overexpression, flow cytometry cell cycle analysis Biochemical and biophysical research communications Medium 17467662
2009 Etv4 and Etv5 are positively regulated by GDNF/Ret signaling in ureteric bud tips; mice lacking both Etv4 alleles and one Etv5 allele show renal agenesis/hypodysplasia, and double homozygous knockouts have complete renal failure; Etv4/Etv5 are required for expression of Cxcr4, Myb, Met, and Mmp14 in the ureteric bud. Mouse genetic knockouts (Etv4-/- , Etv5-/-, compound mutants), renal histology, gene expression analysis (Cxcr4, Myb, Met, Mmp14), Ret signaling context Nature genetics High 19898483
2010 PEA3/ETV4 controls proliferation and invasive properties of oesophageal adenocarcinoma cells; a key target gene is MMP-1; the ERK MAP kinase pathway activates PEA3 and drives the ERK-PEA3-MMP-1 signaling axis. siRNA knockdown of PEA3, proliferation and invasion assays, MMP-1 reporter assay, ERK pathway inhibition experiments, ChIP or reporter assays Molecular cancer Medium 21143918
2011 ETV4 (PEA3) acts as a broad coactivator of HIF signaling: ETV4 forms a complex with HIF-1/2α (demonstrated by mammalian two-hybrid and FRET), and the complex is recruited to the PHD2 promoter (confirmed by ChIP); 7.7% of hypoxically induced transcripts require ETV4 for efficient induction. Mammalian two-hybrid assay, FRET, HIF-1α domain mapping, CITED2 overexpression, factor inhibiting HIF depletion, ChIP for ETV4 and HIF-1α at PHD2 promoter, genome-wide expression profiling Nucleic acids research High 22075993
2011 PEA3 (ETV4) directly activates Notch-1 transcription (AP-1-independent) and Notch-4 transcription (c-JUN-dependent) in breast cancer cells; ChIP confirmed PEA3 enrichment on both Notch-1 and Notch-4 promoters; PEA3 recruitment to Notch-4 requires c-JUN. siRNA knockdown of PEA3, RT-PCR and Western blot for Notch receptors, ChIP for PEA3 on Notch-1 and Notch-4 promoters, Notch-4 luciferase reporter assay, TAM-67 and c-Jun siRNA to dissect AP-1 dependency Breast cancer research : BCR High 21679465
2013 Etv4 promotes prostate cancer metastasis downstream of co-activated PI3-kinase/Ras signaling; Etv4 knockdown abrogates the metastatic phenotype of cells derived from Pten-loss/Kras-activation mouse model without affecting primary tumor growth. Genetically engineered mouse model (Pten loss + oncogenic Kras), lineage tracing with fluorescent reporter, Etv4 shRNA knockdown in derived metastatic cell line, in vivo metastasis assays Proceedings of the National Academy of Sciences of the United States of America High 23918374
2013 Etv4 and Etv5 mediate NGF retrograde signaling and axonal growth of DRG sensory neurons; distal axon NGF application induces Etv4/Etv5 mRNA via MEK/ERK pathway; Etv4/Etv5 siRNA knockdown inhibits NGF-induced neurite outgrowth, while overexpression of Etv4 or Etv5 potentiates it. Compartmentalized DRG neuron cultures with distal NGF application, real-time PCR, pharmacological MEK/ERK inhibition, siRNA knockdown, overexpression gain-of-function, neurite outgrowth assay The Journal of neuroscience : the official journal of the Society for Neuroscience High 24089499
2015 Crystal structures of the ETV4 ETS DNA-binding domain, alone and in complex with DNA, revealed that: (1) DNA backbone contacts account for most binding affinity; (2) a coordinated water network mediates base selection upstream of the GGAA core; (3) ETV4 crystallizes as a disulfide-linked dimer via a novel interface, and reduction to monomers increases DNA binding affinity 40–200-fold, revealing a redox-dependent regulatory mechanism. X-ray crystallography (crystal structures alone and in complex with DNA), disulfide bond reduction experiments, DNA-binding affinity measurements The Journal of biological chemistry High 25866208
2015 Etv4 and Etv5 are specifically expressed in undifferentiated ES cells downstream of Oct3/4; double knockout reduces ES cell proliferation (with upregulation of CDK inhibitors p16/p19, p15, p57) and impairs induction of ectoderm differentiation markers; Etv4/Etv5 regulate stem cell genes Tcf15 and Gbx2. ES cell double knockout by gene targeting, proliferation assay, flow cytometry, embryoid body differentiation assay, microarray gene expression analysis, rescue by Etv4/Etv5 re-expression The Journal of biological chemistry Medium 26224636
2015 ACLY and ACC1 regulate ETV4 protein levels via α-ketoglutarate under hypoxia; loss of ACLY/ACC1 paradoxically increases α-ketoglutarate under hypoxia, which reduces ETV4 expression and activity likely via an epigenetic mechanism; ETV4 knockdown recapitulates the anti-apoptotic transcriptional program of ACLY/ACC1 depletion. Genome-wide shRNA screen, ETV4 siRNA knockdown, metabolomics (α-ketoglutarate measurement), α-ketoglutarate supplementation, transcriptional profiling, apoptosis assays PLoS genetics Medium 26452058
2016 Ret and Etv4 signaling promote directed cell movements (rather than proliferation) of ureteric bud tip progenitor cells during renal branching morphogenesis; Etv4-/- cells tend to lag behind wild-type sister cells and contribute only to trunks rather than tips. Mosaic Analysis with Double Markers (MADM) for single-cell lineage tracing in Etv4 mutant/wild-type chimeric kidneys, time-lapse organ culture imaging PLoS biology High 26894589
2017 ETV4 interacts with MED25 (Mediator subunit 25) through two independent regions: the N-terminal activation domain (AD) and the ETS DNA-binding domain (DBD); the DBD can simultaneously contact all three MED25 sites while the AD contacts one site, creating a high-affinity multivalent interaction; MED25 stimulates ETV4 DNA binding by relieving autoinhibition; ETV4 and MED25 co-occupy enhancers in prostate cancer cells and are jointly required for target gene transcription. NMR chemical shift perturbation, ITC/SPR binding kinetics, domain mapping, crystal structure context, ChIP-seq for ETV4 and MED25, siRNA knockdown + gene expression in prostate cancer cells Journal of molecular biology High 28728983
2017 ETV4 (and ETV1/ETV5) DNA binding is autoinhibited by two independent inhibitory regions flanking the ETS domain: a C-terminal α-helix that packs against the ETS domain and perturbs the DNA-recognition helix (resolved by crystal structure), and an intrinsically disordered N-terminal inhibitory domain (NID) that makes transient intramolecular contacts with the DNA-recognition helix (resolved by NMR); acetylation of lysines in the NID activates DNA binding. Crystal structures of ETV1/4/5, NMR spectroscopy, deletion mutagenesis, acetylation functional assays Nucleic acids research High 28161714
2017 ERK kinase phosphorylates ETV4 at Ser73, which blocks ETV4 binding to the E3 ubiquitin ligase COP1, thereby preventing ubiquitination and proteasomal degradation of ETV4 and stabilizing the protein. ERK activation/inhibition experiments, Western blot for ETV4 protein levels, site-directed mutagenesis (Ser73), co-immunoprecipitation of ETV4-COP1, ubiquitination assay Biochemical and biophysical research communications Medium 28373072
2017 ETV4 directly regulates Cyclin D1 (CCND1) transcription to promote G1-to-S phase cell cycle progression in pancreatic cancer cells; forced Cyclin D1 expression rescues growth inhibition caused by ETV4 silencing. shRNA-mediated ETV4 silencing in ASPC1 and Colo357 cells, ectopic ETV4 expression in BXPC3 cells, reporter assay and ChIP for Cyclin D1 promoter, flow cytometry cell cycle analysis, rescue by Cyclin D1 re-expression Molecular cancer research : MCR Medium 29117940
2018 CIC (Capicua) transcriptionally represses ETV4; loss of CIC leads to ETV4 upregulation, which in turn induces MMP1 expression; MMP1 knockdown completely blocks CIC-deficiency-induced HCC cell proliferation and invasion, establishing the CIC-ETV4-MMP1 axis. CIC overexpression/knockdown in HCC cells, RT-PCR/Western blot for ETV4 and MMP1, MMP1 siRNA rescue, in vivo tumor growth assay Hepatology (Baltimore, Md.) Medium 29251790
2018 ETV4 directly regulates MMP13 transcription in mammary epithelial cells; MMP13 contributes to ETV4-induced proliferation, migration, invasion, and anchorage-independent growth; MMP13 inhibition blocks tumor formation induced by ETV4 in immunodeficient mice. MMP13 promoter-luciferase reporter assays with ETV4 constructs, MMP13 overexpression/knockdown rescue experiments, in vitro proliferation/migration/invasion assays, in vivo xenograft tumorigenicity assay Breast cancer research : BCR High 29996935
2019 PBK kinase enhances the binding of ETV4 to the uPAR promoter (shown by ChIP), increasing uPAR expression and HCC cell migration/invasion; ETV4 is the transcription factor directly binding the core uPAR promoter region. ChIP assay for ETV4 on uPAR promoter ± PBK, PBK gain/loss-of-function, uPAR overexpression rescue in PBK knockdown, orthotopic mouse model Cancer letters Medium 30914208
2019 Phosphorylation of ETV4 at tyrosine 392 by tyrosine kinase PTK6 increases nuclear translocation of ETV4 and is essential for its function in promoting CXCL1/8 expression, tumor-associated neutrophil recruitment, lymphangiogenesis, and lymph node metastasis in bladder cancer. PTK6-ETV4 interaction and phosphorylation assay, Y392 site-directed mutagenesis, nuclear/cytoplasmic fractionation, CXCL1/8 reporter assay, in vivo lymph node metastasis models Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 36670069
2019 ETV4 transcriptionally upregulates ZEB1 (a strong EMT inducer) via the S100A8/A9-MCAM-ETV4 axis in breast cancer cells, driving epithelial-mesenchymal transition, tumor growth, and lung metastasis. siRNA knockdown of MCAM and ETV4, Western blot and RT-PCR for ZEB1 and EMT markers, luciferase reporter assay for ZEB1 promoter, in vivo xenograft and metastasis assays Neoplasia (New York, N.Y.) Medium 31100639
2019 ETV4 directly regulates PXN (paxillin) and MMP1 transcription in non-small cell lung cancer; ETV4-driven proliferation and migration are partially abolished by PXN and/or MMP1 inhibition. Microarray gain/loss-of-function, luciferase reporter assay for PXN and MMP1 promoters, siRNA knockdown of PXN and MMP1, proliferation and migration assays Molecular carcinogenesis Medium 31670855
2019 ETV4 transcriptionally upregulates MSI2 by directly binding to its promoter (confirmed by ChIP and luciferase reporter), promoting lung adenocarcinoma proliferation and invasion; ectopic MSI2 rescues the effects of ETV4 knockdown. ChIP assay for ETV4 at MSI2 promoter, luciferase reporter assay, ETV4 shRNA knockdown, MSI2 re-expression rescue, CCK8/invasion assays Biochemical and biophysical research communications Medium 31253395
2020 ETV4 deletion (CRISPR/Cas9) in endometrial cancer cells greatly reduces estrogen receptor (ER) genomic binding at the majority of ER-bound loci, dampens the gene expression response to estradiol, reduces chromatin accessibility at some ER-bound loci, and impairs ER nuclear translocation; ETV4 loss decreases estrogen-dependent growth in 3D culture and in vivo. CRISPR/Cas9 homozygous ETV4 deletion, ChIP-seq for ER binding, RNA-seq after estradiol treatment, ATAC-seq for chromatin accessibility, nuclear translocation assay, 3D organoid culture, in vivo estrogen-dependent growth assay Cancer research High 32046982
2020 ETV4 directly binds the FOSL1 promoter to increase FOSL1 expression in clear cell renal cell carcinoma via an AKT-dependent manner; the ETV4/FOSL1 axis promotes ccRCC cell migration and metastasis. ChIP for ETV4 on FOSL1 promoter, reporter assay, AKT inhibition experiments, in vitro migration/invasion assays, in vivo metastasis assay Cancer letters Medium 32305558
2020 ETV4 directly binds the CDKN1A (p21) promoter at -704/-696 bp upstream of TSS (confirmed by ChIP and luciferase assay) to repress p21 expression; ETV4 also reduces p53 protein levels; in a transgenic mouse model of prostate-specific ETV4 expression, both p21 and p27 are decreased and prostatic intraepithelial neoplasia develops. Transgenic mouse model (prostate-specific ETV4), ChIP for ETV4 at CDKN1A promoter, luciferase reporter assay with CDKN1A promoter, Western blot for p21/p27/p53 in mouse prostate Journal of hematology & oncology High 32791988
2021 ETV4 and ETV5 are expressed in synovial sarcoma downstream of FGFR signaling (driven by SS18-SSX fusion); ETV4/ETV5 knockdown inhibits synovial sarcoma growth primarily through cell cycle control, and causes striking upregulation of DUX4 and its transcriptional targets. FGFR genetic knockout models, FGFR inhibitor BGJ398 treatment, ETV4/ETV5 siRNA knockdown, transcriptome analysis, FGFR inhibitor + xenograft assays The Journal of clinical investigation Medium 33983905
2021 ETV4 promotes breast cancer stemness by transcriptionally activating glycolytic genes (HK2, LDHA) and CXCR4, thereby activating Sonic Hedgehog signaling; ETV4 knockdown reduces glucose uptake, lactate release, and BCSC maintenance. ETV4 knockdown/overexpression, glucose uptake and lactate assays, CXCR4 promoter reporter assay, sphere formation assay for stemness, xenograft assay Cell death discovery Medium 34052833
2021 ETV4 directly binds the CXCR5 promoter to increase CXCR5 expression in pancreatic ductal adenocarcinoma; CXCL13 increases ETV4 expression via ERK1/2 pathway; the CXCL13/ETV4/CXCR5 axis forms a positive feedback loop promoting PDAC invasion and metastasis. ChIP for ETV4 on CXCR5 promoter, CXCR5 promoter luciferase reporter, ERK1/2 pathway inhibition, CXCR5 knockdown epistasis, CXCR5-neutralizing antibody, in vivo metastasis assay Cancer letters Medium 34582976
2022 ETV4 interacts directly with YAP; this interaction increases nuclear YAP accumulation and directly augments YAP/TEAD4-mediated transcriptional activation; the ETV4-YAP complex activates CXCL1 and CXCL5 to promote myeloid cell recruitment and tumor immune evasion in HCC. Co-immunoprecipitation (ETV4-YAP interaction), nuclear fractionation, luciferase reporter for YAP/TEAD4 targets, ChIP, in vivo transplanted tumor models with immune cell profiling Cancer letters Medium 35296440
2022 HBx (HBV X protein) increases chromatin accessibility at the ETV4 locus via H3K27ac super-enhancer formation, upregulating ETV4 expression; elevated ETV4 then promotes HCC cell invasion and metastasis by transcriptionally upregulating DVL2 and activating Wnt/β-catenin signaling. H3K27ac ChIP-seq (super-enhancer mapping), RNA-seq, DVL2 reporter/Western blot, Wnt/β-catenin pathway readouts, in vitro invasion assays Cell death & disease Medium 35121725
2023 ETV4 transcriptionally activates PD-L1 and CCL2 expression in HCC cells, increasing tumor-associated macrophage and MDSC infiltration and inhibiting CD8+ T-cell accumulation; FGF19/FGFR4 and HGF/c-MET upregulate ETV4 via ERK1/2 pathway; ETV4 also upregulates FGFR4, creating a FGF19-ETV4-FGFR4 positive feedback loop. ETV4 overexpression/knockdown in HCC cell lines, luciferase reporter assay for PD-L1 and CCL2 promoters, orthotopic mouse models, flow cytometry and immunofluorescence for immune cell profiling, ERK1/2 inhibition, CCR2 inhibitor treatment Journal of hepatology Medium 36907560
2023 ETV4 controls HK1 expression to regulate glycolysis-lactate production and thereby activates mTORC1 by relieving TSC2 repression of Rheb; when ETV4 is targeted and low-lactate stress ensues, HDAC6 deacetylates TSC2 (stabilizing it), and G3BP2 recruits lysosomal-TSC2 to suppress mTORC1; HDAC6-G3BP2 complex is required for this adaptive stress response. ETV4 knockdown in NSCLC cells, HK1 reporter assay, lactate/mTORC1 activity measurements, HDAC6-G3BP2 co-IP, TSC2 deacetylation and stability assays, lysosomal fractionation, perinuclear mTOR distribution imaging Oncogene Medium 36823378
2023 ETV4 transcriptionally activates TNF-α and MAPK11 expression; hepatocyte-specific ETV4 knockout reduces DEN-CCL4-induced HCC development and decreases hepatic TNF-α, MAPK11, and macrophage accumulation, while hepatocyte-specific ETV4 transgenic expression promotes HCC growth. Hepatocyte-specific ETV4 knockout (ETV4fl/fl, alb-cre) and transgenic (ETV4Hep-TG) mice, DEN-CCL4 HCC model, luciferase reporter for TNF-α and MAPK11 promoters, immunoblotting, histology Cancer communications (London, England) High 37670477
2024 ETV4 binds to IKZF1-bound enhancers in multiple myeloma cells and maintains MYC and other oncogene expression after IMiD-mediated IKZF1 depletion; CRISPR/Cas9 ablation of ETV4 sensitizes IMiD-resistant MM cells, establishing ETV4 as a mediator of transcriptional plasticity and IMiD resistance. ChIP-seq for ETV4 and IKZF1, CRISPR/Cas9 ETV4 deletion, gene expression analysis, cell viability assays in IMiD-resistant vs sensitive cells Blood cancer discovery Medium 37934799

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer research 362 16585160
2001 Zebrafish pea3 and erm are general targets of FGF8 signaling. Current biology : CB 223 11413000
2002 ETS gene Pea3 controls the central position and terminal arborization of specific motor neuron pools. Neuron 201 12372283
1991 Essential AP-1 and PEA3 binding elements in the human urokinase enhancer display cell type-specific activity. Oncogene 182 1923525
2009 Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis. Nature genetics 179 19898483
2023 FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2. Journal of hepatology 175 36907560
1997 HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer. Oncogene 146 9380403
1995 Ets-related protein E1A-F can activate three different matrix metalloproteinase gene promoters. Oncogene 144 7731700
2016 Evaluation of ETV4 and WT1 expression in CIC-rearranged sarcomas and histologic mimics. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 139 27443513
1997 Differential expression patterns of the PEA3 group transcription factors through murine embryonic development. Oncogene 130 9285689
1996 A single ets-related transcription factor, E1AF, confers invasive phenotype on human cancer cells. Oncogene 120 8570199
2013 ETV4 promotes metastasis in response to activation of PI3-kinase and Ras signaling in a mouse model of advanced prostate cancer. Proceedings of the National Academy of Sciences of the United States of America 117 23918374
2001 The pea3 subfamily ets genes are required for HER2/Neu-mediated mammary oncogenesis. Current biology : CB 116 11719215
2004 Expression of SRC-1, AIB1, and PEA3 in HER2 mediated endocrine resistant breast cancer; a predictive role for SRC-1. Journal of clinical pathology 112 15452162
2023 ETV4 Mediated Tumor-Associated Neutrophil Infiltration Facilitates Lymphangiogenesis and Lymphatic Metastasis of Bladder Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 111 36670069
2001 PEA3 is up-regulated in response to Wnt1 and activates the expression of cyclooxygenase-2. The Journal of biological chemistry 110 11274170
2003 Role for ETS domain transcription factors Pea3/Erm in mouse lung development. Developmental biology 102 12941618
2002 FGF signaling regulates expression of Tbx2, Erm, Pea3, and Pax3 in the early nasal region. Developmental biology 102 12086464
2004 Ets gene PEA3 cooperates with beta-catenin-Lef-1 and c-Jun in regulation of osteopontin transcription. The Journal of biological chemistry 86 14990565
1997 Structure-function relationships of the PEA3 group of Ets-related transcription factors. Biochemical and molecular medicine 85 9259977
2019 PBK overexpression promotes metastasis of hepatocellular carcinoma via activating ETV4-uPAR signaling pathway. Cancer letters 78 30914208
2000 Hepatocyte growth factor upregulates E1AF that induces oral squamous cell carcinoma cell invasion by activating matrix metalloproteinase genes. Carcinogenesis 77 10836994
2018 Capicua suppresses hepatocellular carcinoma progression by controlling the ETV4-MMP1 axis. Hepatology (Baltimore, Md.) 76 29251790
2016 Ret and Etv4 Promote Directed Movements of Progenitor Cells during Renal Branching Morphogenesis. PLoS biology 76 26894589
2004 Elevated beta1,4-galactosyltransferase I in highly metastatic human lung cancer cells. Identification of E1AF as important transcription activator. The Journal of biological chemistry 75 15611127
2003 Association of ets-related transcriptional factor E1AF expression with tumour progression and overexpression of MMP-1 and matrilysin in human colorectal cancer. The Journal of pathology 68 12898592
2000 The PEA3 group of ETS-related transcription factors. Role in breast cancer metastasis. Advances in experimental medicine and biology 68 10959416
1998 The PEA3 Ets transcription factor is a downstream target of the HER2/Neu receptor tyrosine kinase. Oncogene 64 9467955
2020 Function and regulation of the PEA3 subfamily of ETS transcription factors in cancer. American journal of cancer research 63 33163259
1997 Cooperation of two PEA3/AP1 sites in uPA gene induction by TPA and FGF-2. Gene 62 9409785
2021 ETV4 promotes breast cancer cell stemness by activating glycolysis and CXCR4-mediated sonic Hedgehog signaling. Cell death discovery 59 34052833
2019 ETV4 overexpression promotes progression of non-small cell lung cancer by upregulating PXN and MMP1 transcriptionally. Molecular carcinogenesis 59 31670855
2010 Overlapping functions of Pea3 ETS transcription factors in FGF signaling during zebrafish development. Developmental biology 59 20346941
2003 Expression of ets-related transcriptional factor E1AF is associated with tumor progression and over-expression of matrilysin in human gastric cancer. Carcinogenesis 59 14604892
2020 ETV4 Is Necessary for Estrogen Signaling and Growth in Endometrial Cancer Cells. Cancer research 58 32046982
2015 ETS-related transcription factors ETV4 and ETV5 are involved in proliferation and induction of differentiation-associated genes in embryonic stem (ES) cells. The Journal of biological chemistry 58 26224636
2000 The PEA3 Ets transcription factor comprises multiple domains that regulate transactivation and DNA binding. The Journal of biological chemistry 57 11096072
1999 Expression of the Ets transcription factors erm and pea3 in early zebrafish development. Mechanisms of development 57 10534622
2018 ETV4 transcription factor and MMP13 metalloprotease are interplaying actors of breast tumorigenesis. Breast cancer research : BCR 56 29996935
2003 Function of PEA3 Ets transcription factors in mammary gland development and oncogenesis. Journal of mammary gland biology and neoplasia 56 14635793
2011 NOTCH-1 and NOTCH-4 are novel gene targets of PEA3 in breast cancer: novel therapeutic implications. Breast cancer research : BCR 54 21679465
2010 The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinoma. Molecular cancer 54 21143918
2001 Expression of E1AF/PEA3, an Ets-related transcription factor in human non-small-cell lung cancers: its relevance in cell motility and invasion. International journal of cancer 54 11519038
1997 Antisense E1AF transfection restrains oral cancer invasion by reducing matrix metalloproteinase activities. The American journal of pathology 54 9176403
1996 PEA3 transactivates vimentin promoter in mammary epithelial and tumor cells. Oncogene 54 8895512
1998 Molecular characterization of the zebrafish PEA3 ETS-domain transcription factor. Oncogene 53 9671318
1999 Increased E1AF expression in mouse fibrosarcoma promotes metastasis through induction of MT1-MMP expression. Oncogene 52 10208438
2019 Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness. Neoplasia (New York, N.Y.) 51 31100639
2003 Expression of PEA3/E1AF/ETV4, an Ets-related transcription factor, in breast tumors: positive links to MMP2, NRG1 and CGB expression. Carcinogenesis 50 14633660
2001 Expression patterns of the Ets transcription factors from the PEA3 group during early stages of mouse development. Mechanisms of development 50 11578874
2013 Pea3 transcription factor family members Etv4 and Etv5 mediate retrograde signaling and axonal growth of DRG sensory neurons in response to NGF. The Journal of neuroscience : the official journal of the Society for Neuroscience 49 24089499
2018 Pea3 Transcription Factors, Etv4 and Etv5, Are Required for Proper Hippocampal Dendrite Development and Plasticity. Cerebral cortex (New York, N.Y. : 1991) 48 27909004
2016 Neuropilin-2 promotes tumourigenicity and metastasis in oesophageal squamous cell carcinoma through ERK-MAPK-ETV4-MMP-E-cadherin deregulation. The Journal of pathology 48 27063000
2006 ETV4 and Myeov knockdown impairs colon cancer cell line proliferation and invasion. Biochemical and biophysical research communications 48 16678123
2005 Association of Ets-related transcriptional factor E1AF expression with overexpression of matrix metalloproteinases, COX-2 and iNOS in the early stage of colorectal carcinogenesis. Carcinogenesis 45 15695237
1997 Expression of E1AF, an ets-family transcription factor, is correlated with the invasive phenotype of oral squamous cell carcinoma. Oral oncology 44 9509127
2020 ETV4 is a theranostic target in clear cell renal cell carcinoma that promotes metastasis by activating the pro-metastatic gene FOSL1 in a PI3K-AKT dependent manner. Cancer letters 43 32305558
2024 α-Ketoglutarate alleviates osteoarthritis by inhibiting ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway. Cellular & molecular biology letters 41 38877424
2022 HBx increases chromatin accessibility and ETV4 expression to regulate dishevelled-2 and promote HCC progression. Cell death & disease 41 35121725
2017 ETV4 Facilitates Cell-Cycle Progression in Pancreatic Cells through Transcriptional Regulation of Cyclin D1. Molecular cancer research : MCR 41 29117940
2015 ACLY and ACC1 Regulate Hypoxia-Induced Apoptosis by Modulating ETV4 via α-ketoglutarate. PLoS genetics 41 26452058
2015 Structures of the Ets Protein DNA-binding Domains of Transcription Factors Etv1, Etv4, Etv5, and Fev: DETERMINANTS OF DNA BINDING AND REDOX REGULATION BY DISULFIDE BOND FORMATION. The Journal of biological chemistry 40 25866208
2014 Overexpression of ETV4 protein in triple-negative breast cancer is associated with a higher risk of distant metastasis. OncoTargets and therapy 40 25328406
2005 E1AF/PEA3 activates the Rho/Rho-associated kinase pathway to increase the malignancy potential of non-small-cell lung cancer cells. Cancer research 37 16322223
2024 The Mediating Role of miR-451/ETV4/MMP13 Signaling Axis on Epithelialmesenchymal Transition in Promoting Non-small Cell Lung Cancer Progression. Current molecular pharmacology 36 37489792
2011 Synthetic transactivation screening reveals ETV4 as broad coactivator of hypoxia-inducible factor signaling. Nucleic acids research 36 22075993
2020 KIF2A promotes the progression via AKT signaling pathway and is upregulated by transcription factor ETV4 in human gastric cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 34 32106376
2017 ETV4 and AP1 Transcription Factors Form Multivalent Interactions with three Sites on the MED25 Activator-Interacting Domain. Journal of molecular biology 34 28728983
2015 ETV/Pea3 family transcription factor-encoding genes are overexpressed in CIC-mutant oligodendrogliomas. Genes, chromosomes & cancer 34 26357005
2023 Transcription factor ETV4 promotes the development of hepatocellular carcinoma by driving hepatic TNF-α signaling. Cancer communications (London, England) 33 37670477
2013 Novel 5' fusion partners of ETV1 and ETV4 in prostate cancer. Neoplasia (New York, N.Y.) 32 23814484
2011 ERβ and PEA3 co-activate IL-8 expression and promote the invasion of breast cancer cells. Cancer biology & therapy 32 21266854
1997 Activation of the p21(Waf1/Cip1) promoter by the ets oncogene family transcription factor E1AF. Biochemical and biophysical research communications 32 9223430
2017 Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4 and ETV5. Nucleic acids research 31 28161714
2016 The utility of ETV1, ETV4 and ETV5 RNA in-situ hybridization in the diagnosis of CIC-DUX sarcomas. Histopathology 31 27790742
2024 ETV4-Dependent Transcriptional Plasticity Maintains MYC Expression and Results in IMiD Resistance in Multiple Myeloma. Blood cancer discovery 30 37934799
2022 ETV4 potentiates nuclear YAP retention and activities to enhance the progression of hepatocellular carcinoma. Cancer letters 30 35296440
2021 ETV4 and ETV5 drive synovial sarcoma through cell cycle and DUX4 embryonic pathway control. The Journal of clinical investigation 30 33983905
2019 ETV4 promotes proliferation and invasion of lung adenocarcinoma by transcriptionally upregulating MSI2. Biochemical and biophysical research communications 30 31253395
2004 E1AF, an ets-oncogene family transcription factor. Cancer letters 30 15500943
1998 The genomic breakpoint and chimeric transcripts in the EWSR1-ETV4/E1AF gene fusion in Ewing sarcoma. Cytogenetics and cell genetics 30 9858836
2020 CRLF1-MYH9 Interaction Regulates Proliferation and Metastasis of Papillary Thyroid Carcinoma Through the ERK/ETV4 Axis. Frontiers in endocrinology 29 32982961
2007 E1AF promotes breast cancer cell cycle progression via upregulation of Cyclin D3 transcription. Biochemical and biophysical research communications 29 17467662
2016 Brain-derived neurotrophic factor promotes vesicular glutamate transporter 3 expression and neurite outgrowth of dorsal root ganglion neurons through the activation of the transcription factors Etv4 and Etv5. Brain research bulletin 28 26876757
2021 ETV4 promotes pancreatic ductal adenocarcinoma metastasis through activation of the CXCL13/CXCR5 signaling axis. Cancer letters 27 34582976
2020 ETV4 promotes the progression of gastric cancer through regulating KDM5D. European review for medical and pharmacological sciences 27 32196595
2020 ETV4 promotes late development of prostatic intraepithelial neoplasia and cell proliferation through direct and p53-mediated downregulation of p21. Journal of hematology & oncology 26 32791988
2015 Specific and redundant activities of ETV1 and ETV4 in prostate cancer aggressiveness revealed by co-overexpression cellular contexts. Oncotarget 26 25595908
2006 A positive role for PEA3 in HER2-mediated breast tumour progression. British journal of cancer 26 17060941
2021 Circular RNA hsa_circ_0001666 sponges miR‑330‑5p, miR‑193a‑5p and miR‑326, and promotes papillary thyroid carcinoma progression via upregulation of ETV4. Oncology reports 25 33760216
2017 ETV4 collaborates with Wnt/β-catenin signaling to alter cell cycle activity and promote tumor aggressiveness in gastrointestinal stromal tumor. Oncotarget 25 29371979
2009 Increased PEA3/E1AF and decreased Net/Elk-3, both ETS proteins, characterize human NSCLC progression and regulate caveolin-1 transcription in Calu-1 and NCI-H23 NSCLC cell lines. Carcinogenesis 25 19483189
1992 Expression of a 91-kilodalton PEA3-binding protein is down-regulated during differentiation of F9 embryonal carcinoma cells. Molecular and cellular biology 25 1569949
2014 Pea3 expression promotes the invasive and metastatic potential of colorectal carcinoma. World journal of gastroenterology 24 25516649
2007 Functional interaction of E1AF and Sp1 in glioma invasion. Molecular and cellular biology 24 17938207
2021 ETV4 plays a role on the primary events during the adenoma-adenocarcinoma progression in colorectal cancer. BMC cancer 22 33648461
2017 Phosphorylation of ETV4 at Ser73 by ERK kinase could block ETV4 ubiquitination degradation in colorectal cancer. Biochemical and biophysical research communications 22 28373072
2023 HDAC6-G3BP2 promotes lysosomal-TSC2 and suppresses mTORC1 under ETV4 targeting-induced low-lactate stress in non-small cell lung cancer. Oncogene 21 36823378
2018 Increased ETV4 expression correlates with estrogen-enhanced proliferation and invasiveness of cholangiocarcinoma cells. Cancer cell international 21 29467595
2010 Pea3 transcription factors and wnt1-induced mouse mammary neoplasia. PloS one 21 20107508

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