Affinage

EHF

ETS homologous factor · UniProt Q9NZC4

Length
300 aa
Mass
34.9 kDa
Annotated
2026-04-28
77 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EHF is an epithelium-specific ETS family transcription factor that functions as a context-dependent activator or repressor of target gene promoters to maintain epithelial differentiation, suppress epithelial-to-mesenchymal transition (EMT), and regulate innate immune and inflammatory programs across diverse epithelial tissues (PMID:10644770, PMID:11259407, PMID:22505649, PMID:24142692, PMID:34180969). As a transcriptional repressor, EHF directly binds ETS/AP-1 composite elements to antagonize MAPK-driven transcription and silences EMT drivers (TWIST1, ZEB2), stemness factors (Lin28A/B, Sox9, Oct4), cytokines (IL-6, CXCL1), and receptors (FcεRI, CXCR4), while as an activator it induces E-cadherin, caspase-3, p16(INK4a), SPDEF, and RUVBL1 (PMID:11259407, PMID:18037958, PMID:17627613, PMID:27923832, PMID:27197175, PMID:33674341, PMID:38492894, PMID:21617703). EHF activity is regulated post-translationally by Dclk2-mediated phosphorylation that drives nuclear export, by CpG methylation-mediated silencing, and by upstream NF-κB, TGF-β/Smad, STAT3, and AR signaling; it physically cooperates with cofactors CDX1 (via its PNT domain) and AJUBA to direct chromatin remodeling and transcriptional reprogramming (PMID:38513137, PMID:18037958, PMID:18475289, PMID:33414441, PMID:35606410, PMID:38799645). In mouse genetic models, loss of Ehf causes papillomas, impaired goblet cell and lobuloalveolar differentiation, enhanced colitis susceptibility, and increased tumor incidence, establishing it as a broadly required epithelial homeostasis factor and context-dependent tumor suppressor (PMID:34180969, PMID:38781975, PMID:25606410).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 High

    Identification of EHF as an epithelium-restricted ETS transcription factor with context-dependent transactivation activity established the foundational molecular identity and tissue specificity of the gene.

    Evidence Reporter assays and EMSA on c-MET promoter in transfected cells

    PMID:10527851 PMID:10644770

    Open questions at the time
    • No endogenous target genes confirmed by ChIP at this stage
    • Repressor vs. activator specificity determinants unknown
    • No loss-of-function data
  2. 2001 High

    Demonstrating that EHF represses Ras/MAPK-driven transcription through ETS/AP-1 composite elements and is absent in carcinomas established its dual activator-repressor nature and implicated it as a tumor suppressor.

    Evidence Promoter mutagenesis reporter assays in multiple cell lines plus immunohistochemistry on normal vs. tumor tissue

    PMID:11259407

    Open questions at the time
    • No direct in vivo tumor suppressor evidence
    • Mechanism of repression (cofactor recruitment vs. competition) undefined
  3. 2007 High

    Discovery that EHF directly activates the caspase-3 promoter to induce apoptosis and that its own expression is silenced by CpG methylation in tumors provided the first mechanistic link between EHF loss and cancer cell survival.

    Evidence ChIP on CASP3 promoter, 5-aza-2'-deoxycytidine demethylation rescue, colony and apoptosis assays in prostate cancer cells

    PMID:17627613 PMID:18037958

    Open questions at the time
    • Genome-wide target repertoire unknown
    • Which methyltransferases silence EHF not identified
    • Senescence-related p16 activation mechanism not distinguished from apoptosis pathway
  4. 2008 High

    Identification of NF-κB as a direct upstream activator of EHF transcription placed EHF within inflammatory signaling cascades in airway epithelium.

    Evidence NF-κB binding site mutagenesis in the EHF promoter plus cytokine stimulation in bronchial epithelial cells

    PMID:18475289

    Open questions at the time
    • Whether NF-κB regulation is tissue-general or airway-specific not resolved
    • MAPK vs. NF-κB pathway hierarchy for EHF regulation unclear
  5. 2012 High

    Showing that EHF loss induces EMT and stem-like features by derepressing TWIST1, ZEB2, BMI1, and POU5F1 unified EHF's tumor-suppressive role with epithelial differentiation maintenance.

    Evidence Loss-of-function knockdown with rescue, gene expression analysis, in vivo tumor-initiating assays in prostate cells

    PMID:22505649

    Open questions at the time
    • Direct ChIP binding to each EMT promoter not confirmed for all targets
    • Isoform-specific contributions not dissected
  6. 2013 High

    Genome-wide ChIP-seq in corneal epithelium revealed that EHF directly occupies hundreds of epithelial gene loci with both activating and repressive outputs, establishing the breadth of its transcriptional regulatory network.

    Evidence ChIP-seq combined with transcriptome profiling and loss-of-function in human corneal epithelial cells

    PMID:24142692

    Open questions at the time
    • Cofactor requirements for activation vs. repression not defined genome-wide
    • Overlap of targets across different epithelial tissues not compared
  7. 2016 High

    Multiple studies converged to show EHF directly controls E-cadherin, Lin28A/B-let-7, IL-6/STAT3, HER2/HER3, and ABCB1 promoters, revealing it as a multi-target hub linking differentiation, stemness, inflammation, and drug metabolism.

    Evidence ChIP-confirmed promoter binding with reporter assays in prostate, pancreatic, thyroid, and intestinal cells; in vivo xenograft validation

    PMID:27197175 PMID:27517321 PMID:27567379 PMID:27732936 PMID:27923832

    Open questions at the time
    • How EHF selects among different targets in different tissues not resolved
    • Structural basis of promoter recognition beyond ETS motif unknown
  8. 2017 High

    ChIP-seq in bronchial epithelium extended the target repertoire to wound repair and inflammation genes and showed EHF activates SPDEF to drive goblet cell differentiation, linking EHF to mucosal defense.

    Evidence ChIP-seq and RNA-seq after EHF depletion in primary human bronchial epithelial cells, wound closure assay

    PMID:28461336

    Open questions at the time
    • Whether EHF directly interacts with SPDEF protein or only activates its transcription unclear
    • In vivo airway phenotype of EHF loss not yet tested
  9. 2021 High

    Genetic deletion of Ehf in mice produced papillomas, corneal ulcers, colitis susceptibility, goblet cell loss, and enhanced adenoma development, providing definitive in vivo proof that the ETS DNA-binding domain is essential for epithelial homeostasis and tumor suppression.

    Evidence Novel Ehf knockout mouse strains with histopathology, experimental colitis, and Apc-initiated tumor model

    PMID:34180969

    Open questions at the time
    • Tissue-specific vs. systemic contributions not fully dissected with conditional knockouts at this stage
    • Whether observed phenotypes are cell-autonomous in all tissues not confirmed
  10. 2021 High

    Discovery that the short EHF isoform (EHF-SF) specifically promotes ETS1 protein degradation to block ZEB1 transcription, while a point mutant acts as a dominant-negative to enhance metastasis, revealed isoform-specific and gain-of-function mechanisms.

    Evidence Reporter assays, protein degradation assays, mutagenesis, in vivo metastasis models

    PMID:33712555

    Open questions at the time
    • Proteasomal vs. lysosomal degradation pathway for ETS1 not specified
    • Relative abundance and regulation of EHF-LF vs. EHF-SF isoforms in normal tissues unknown
  11. 2021 High

    Placement of EHF downstream of AR signaling showed that androgen deprivation silences EHF, derepressing EZH2 and promoting neuroendocrine differentiation via H3K27me3, linking EHF loss to treatment-resistant prostate cancer.

    Evidence ChIP for AR binding at EHF locus, EZH2 inhibitor epistasis, mouse and cell models

    PMID:33414441

    Open questions at the time
    • Whether EHF directly binds the EZH2 promoter or acts indirectly not resolved
    • Clinical correlation with neuroendocrine differentiation markers not fully established
  12. 2022 High

    EHF's physical interaction with CDX1 via its PNT domain and their cooperative induction of chromatin remodeling established that EHF functions through cofactor partnerships to drive colonic differentiation, not solely through autonomous DNA binding.

    Evidence Co-immunoprecipitation with domain mapping, CRISPR compound knockout mice, ATAC-seq and RNA-seq

    PMID:35606410

    Open questions at the time
    • Whether PNT domain mediates additional cofactor interactions not explored
    • Structural basis of EHF-CDX1 interaction unknown
  13. 2024 High

    Identification of Dclk2-mediated phosphorylation of EHF causing nuclear export established the first post-translational mechanism controlling EHF subcellular distribution and transcriptional output.

    Evidence Co-IP, immunofluorescence for nucleoplasmic distribution, ChIP on caspase promoters, OGD/CCI models

    PMID:38513137

    Open questions at the time
    • Phosphorylation site(s) on EHF not mapped
    • Whether this kinase-substrate relationship operates in epithelial tissues not tested
  14. 2024 High

    EHF deficiency was shown to upregulate CXCL1, recruiting CXCR2+ neutrophils and reshaping the pancreatic tumor microenvironment — extending EHF's tumor-suppressive role from cell-autonomous to immune-regulatory.

    Evidence ChIP, Ehf-knockout mice, syngeneic models, single-cell RNA-seq, CXCL1/CXCR2 blockade rescue

    PMID:38492894

    Open questions at the time
    • Whether EHF regulates additional chemokines systemically not surveyed
    • Human clinical validation of neutrophil recruitment phenotype lacking
  15. 2024 Medium

    Discovery that EHF forms liquid-like nuclear condensates that repress TERT, IL-6, and CXCL12 introduced phase separation as a mechanism for EHF-mediated transcriptional repression and senescence induction without SASP.

    Evidence CRISPR library screening, phase separation assays, ChIP, telomere length measurement, bilobetin drug screen

    PMID:39710057

    Open questions at the time
    • Biophysical parameters of EHF condensates (saturation concentration, IDR contributions) not characterized
    • Whether condensate formation occurs in normal epithelial cells or is cancer-specific unknown
    • Independent replication needed
  16. 2025 High

    EHF was shown to regulate dendritic cell maturation by directly controlling Ccr7, PD-L1, Irf4, and Rel expression, demonstrating a non-epithelial immune cell-autonomous role in shaping adaptive immune responses.

    Evidence Conditional DC-specific Ehf knockout mice, CUT&TAG, single-cell RNA-seq, T cell polarization assays, autoimmune/tumor models

    PMID:41730908

    Open questions at the time
    • Whether EHF functions in other immune cell lineages not tested
    • Human DC relevance not confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of EHF's activator-repressor switch, the full spectrum of phosphorylation sites governing its nuclear-cytoplasmic shuttling, whether phase separation is a general EHF mechanism in normal epithelia, and the complete set of PNT domain-mediated cofactor interactions.
  • No crystal or cryo-EM structure of EHF or its complexes
  • Systematic mapping of EHF post-translational modifications not performed
  • Tissue-specific isoform expression and regulation not comprehensively characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 21 GO:0003677 DNA binding 13
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-74160 Gene expression (Transcription) 15 R-HSA-1643685 Disease 10 R-HSA-162582 Signal Transduction 7 R-HSA-1266738 Developmental Biology 5 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 3
Partners
AJUBACBPCDX1DCLK2EP300ETS1RRAD

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 EHF (ESE-3) is an epithelium-specific ETS transcription factor that transactivates the c-MET promoter via three high-affinity binding sites, and shows different promoter transactivation specificity from ESE-1 despite similar DNA-binding affinity, indicating context-dependent transcriptional activity. Transient transfection reporter assays, DNA-binding/EMSA, promoter analysis The Journal of biological chemistry High 10644770
2001 EHF (ESE-3) acts as a context-dependent transcriptional repressor of Ras/phorbol ester-induced promoters containing ETS and AP-1 binding sites, repressing MAPK signaling-driven transcription in a sequence- and arrangement-dependent manner; it is a nuclear protein expressed exclusively in differentiated epithelial cells and absent in epithelial carcinomas. Transient transfection reporter assays, immunohistochemistry with monoclonal antibody, promoter mutagenesis The Journal of biological chemistry High 11259407
1999 EHF protein represses the ETS-2-induced transcriptional activity of stromelysin-1 and collagenase-1 promoters, demonstrating transcriptional repressor activity on matrix metalloproteinase promoters. Transient transfection reporter assays Biochemical and biophysical research communications Medium 10527851
2002 ESE-3/EHF cytokine-induced expression in bronchial smooth muscle cells is mediated through MEK1/2 and p38 MAPK signaling pathways, and overexpression of ESE-3 inhibits MMP-1 promoter activity, indicating it acts as a transcriptional repressor downstream of these kinases. Pharmacological inhibitors (U0126, SB03580), reporter assays, RT-PCR, Western blot American journal of respiratory cell and molecular biology Medium 12444029
2007 EHF (ESE-3) re-expression in prostate cancer cells inhibits clonogenic survival and induces apoptosis by directly binding the caspase-3 (CASP3) promoter and increasing procaspase-3 levels, acting as a tumor suppressor; ESE-3 silencing in tumorigenic cells is mediated by CpG methylation of an evolutionarily conserved site in its promoter. Chromatin immunoprecipitation, reporter assay, re-expression experiments, 5-aza-2'-deoxycytidine treatment, colony assay, apoptosis assay Oncogene High 18037958
2007 ESE-3/EHF is upregulated in cellular senescence downstream of p38 MAPK signaling; ectopic expression induces growth retardation, increased SA-β-gal activity, and upregulation of p16(INK4a) via direct binding of recombinant ESE-3 to ETS-binding sequences in the p16(INK4a) promoter. Microarray, reporter assay, recombinant protein EMSA, SA-β-gal assay, Western blot Cancer science High 17627613
2008 EHF/ESE-3 expression in airway epithelial cells is upregulated by IL-1β and TNF-α via NF-κB activation; NF-κB binding sequences in the ESE-3 promoter are required for cytokine-induced expression, and ESE-1 further upregulates ESE-3 expression. Promoter characterization, NF-κB binding site mutagenesis, reporter assays, RT-PCR Cell research High 18475289
2011 EHF directly activates transcription of RUVBL1, an ATPase associated with chromatin-remodeling complexes; RUVBL1 in turn represses p53 and its target genes by binding the p53 promoter, interfering with RNF20/hBRE1-mediated histone H2B monoubiquitination and promoting PAF1-mediated H3K9 trimethylation, thereby blocking p53-mediated apoptosis in colon tumor cells. Chromatin immunoprecipitation, reporter assays, siRNA knockdown, histone modification analysis, apoptosis assays EMBO reports High 21617703
2012 ESE3/EHF represses transcription of key EMT and cancer stem cell genes including TWIST1, ZEB2, BMI1, and POU5F1 in prostate epithelial cells; loss of ESE3/EHF induces EMT, stem-like features, and tumor-initiating properties, which are reversed by re-expression of ESE3/EHF. Loss-of-function knockdown, re-expression, gene expression analysis, in vitro and in vivo tumor assays Cancer research High 22505649
2013 EHF promotes cornea epithelial fate through complementary gene-activating and -repressing activities, and potential interactions with KLF4 and KLF5 were identified; EHF occupancy at target gene loci was determined by ChIP-seq. Loss-of-function studies, ChIP-seq, transcriptome profiling The Journal of biological chemistry High 24142692
2013 Ectopic expression of EHF in intestinal epithelial cells activates HCK-dependent apical-to-basolateral transcytosis of non-opsonized and SIgA-opsonized particles in a follicle-associated epithelium model, placing EHF upstream of HCK in regulating mucosal antigen sampling. Ectopic expression, transcytosis assays, kinase inhibitor studies The Journal of biological chemistry Medium 23439650
2015 EHF is upregulated by TGF-β/Smad signaling in mast cells; forced EHF expression represses transcription of FcεRIα, FcεRIβ, and c-Kit genes by directly binding their promoters, reducing surface FcεRI and c-Kit, suppressing degranulation and cytokine production, and decreasing GATA1, GATA2, and Stat5b expression. Forced expression, promoter-binding assays (ChIP), reporter assays, flow cytometry, degranulation assays Journal of immunology High 26297757
2016 ESE3/EHF binds and represses the Lin28A and Lin28B gene promoters while activating transcription and maturation of let-7 microRNAs in normal prostate cells; loss of ESE3/EHF upregulates Lin28A/B and downregulates let-7, driving prostate cancer stem cell expansion. ChIP, promoter reporter assays, microRNA profiling, siRNA knockdown, xenograft models Cancer research High 27197175
2016 ESE3/EHF directly binds a novel ETS binding site in the IL-6 gene promoter and represses IL-6 transcription; loss of ESE3/EHF activates IL-6/JAK/STAT3 signaling, promoting stem-like transformation in prostate epithelial cells. ChIP, reporter assays, siRNA knockdown, IL-6 inhibition rescue experiments Oncotarget High 27732936
2016 ESE3/EHF inhibits pancreatic cancer metastasis by directly upregulating E-cadherin transcription; knockdown of ESE3 promotes cell motility and invasiveness in vitro and metastasis in an orthotopic mouse model. Reporter assays, ChIP, siRNA knockdown, orthotopic mouse model, immunohistochemistry Cancer research High 27923832
2016 EHF transcriptionally regulates HER2 (ERBB2) and HER3 (ERBB3) in thyroid cancer cells, contributing to PI3K/Akt and MAPK/Erk pathway activation; this was confirmed by dual-luciferase reporter and ChIP assays. ChIP, dual-luciferase reporter assay, siRNA knockdown, ectopic expression, in vivo xenograft Oncotarget High 27517321
2017 EHF ChIP-seq in primary human bronchial epithelial cells shows enrichment of EHF targets in inflammation and wound repair genes; EHF depletion alters epithelial secretion of a neutrophil chemokine, slows wound closure, and EHF activates SPDEF expression contributing to goblet cell hyperplasia. ChIP-seq, RNA-seq after EHF depletion, wound closure assay, cytokine secretion assay The Journal of biological chemistry High 28461336
2019 miR-365-3p targets EHF 3'UTR to decrease EHF protein expression; EHF acts as a transcription factor for KRT16 in oral squamous cell carcinoma, and EHF-driven KRT16 expression promotes β5-integrin/c-Met signaling and downstream Src/STAT3/FAK/ERK pathway activation. Dual-luciferase reporter (miRNA targeting), ectopic expression, siRNA knockdown, confocal colocalization, in vitro/in vivo models Journal of experimental & clinical cancer research High 30782177
2020 EHF directly upregulates TGF-β1 transcription in colorectal cancer cells, thereby activating canonical TGF-β signaling to promote tumor cell proliferation, migration, and invasion. Reporter assays, ChIP, siRNA knockdown, ectopic expression, in vitro and in vivo functional assays Cancer science High 32372436
2021 EHF produces two transcript variants (EHF-LF including exon 1, EHF-SF excluding exon 1); only EHF-SF abrogates ETS1-mediated activation of the ZEB1 promoter by promoting degradation of ETS1 protein, thereby inhibiting EMT. A point mutation in the EHF ETS domain abolishes this function and creates a dominant-negative form that enhances metastasis in vivo. Reporter assays, protein degradation assays, in vivo metastasis models, mutagenesis Oncogenesis High 33712555
2021 EHF suppresses pancreatic cancer stemness by directly repressing CXCR4 transcription, decreasing cancer cell sensitivity to CXCL12 from pancreatic stellate cells; EHF also has a cell-autonomous role repressing Sox9, Sox2, Oct4, and Nanog transcription. Rosiglitazone upregulates EHF to suppress cancer stemness. ChIP, luciferase reporter assays, sphere formation assays, flow cytometry, in vivo KPC mouse model Gut High 33674341
2021 Loss of EHF promotes neuroendocrine differentiation in prostate cancer via ADT/AR/EHF/EZH2 signaling: androgen deprivation reduces EHF expression by relieving AR binding to androgen-responsive elements in the EHF locus, which promotes EZH2 expression and enzymatic activity, leading to H3K27me3-mediated transcriptional repression of downstream genes. ChIP, siRNA/shRNA knockdown, EZH2 inhibitor, cell and mouse models, Western blot Cell death & disease High 33414441
2021 EBV protein LMP2A causes upregulation of EHF via phosphorylation of STAT3 in gastric cancer cells; EHF knockdown inhibits cell proliferation and regulates cancer pathway genes including FZD5; EHF motif is enriched in activated enhancers in EBV-positive gastric cancer. STAT3 knockdown rescue by EHF overexpression, genome-wide active histone ChIP-seq, siRNA knockdown, immunostaining Cancer science Medium 34014591
2021 Ese-3/EHF promotes colon cancer cell proliferation by downregulating EHD2 and transactivating INPP4B as direct downstream target genes. siRNA knockdown, ectopic expression, in vitro/in vivo proliferation assays American journal of cancer research Medium 33520362
2022 EHF physically interacts with CDX1 via its PNT domain; EHF and CDX1 co-operatively drive transcription of the colonic differentiation marker VIL1; compound deletion of Ehf and Cdx1 in mouse colon disrupts normal colonic differentiation and enhances colorectal tumor progression. Re-expression of EHF and CDX1 induces extensive chromatin remodeling and transcriptional reprogramming. Co-immunoprecipitation (PNT domain interaction), reporter assays, CRISPR knockout mouse model, ATAC-seq, RNA-seq Cell death and differentiation High 35606410
2021 Deletion of the EHF ETS DNA-binding domain in mice causes epidermal papillomas, preputial/vulval abscesses, corneal ulcers, increased susceptibility to colitis, impaired goblet cell differentiation, and enhanced Apc-initiated adenoma development, demonstrating that the DNA-binding domain is essential for postnatal epithelial homeostasis. Novel Ehf knockout mouse strains (Ehf-/- and gut-specific), histopathology, experimental colitis model, transcriptomic profiling Development (Cambridge, England) High 34180969
2024 EHF deficiency in pancreatic cancer induces CXCL1 transcription, enhancing CXCR2+ neutrophil recruitment in a CXCL1-CXCR2-dependent manner; TP53 mutation-mediated loss of EHF drives this process. Nifurtimox elevates tumoral EHF and inhibits JAK1/STAT1 pathway, suppressing CXCR2+ neutrophil recruitment. ChIP assay, Ehf-knockout mice, syngeneic mouse models, multiplexed cytokine assay, flow cytometry, single-cell RNA-seq Gastroenterology High 38492894
2024 Dclk2 phosphorylates EHF, changing its nucleoplasmic distribution by causing p-EHF to exit the nucleus, thereby decreasing nuclear EHF levels; nuclear EHF binds the promoters of Caspase1 and Caspase3 to reduce their transcription and inhibit neuronal pyroptosis. Cpeb4 upregulates Dclk2 by increasing Dclk2 mRNA stability. Promoter binding assays, ChIP, co-immunoprecipitation, immunofluorescence for nucleoplasmic distribution, OGD cell model, CCI mouse model, knockdown experiments Journal of cerebral blood flow and metabolism High 38513137
2024 EHF transcriptionally activates GLI1 and CCL2 in cholangiocarcinoma; EHF-driven CCL2 recruits and activates tumor-associated macrophages via the CCL2/CCR2 axis, remodeling the tumor microenvironment. ChIP, reporter assays, in vitro and in vivo functional experiments, immunohistochemistry MedComm High 38741887
2024 EHF interacts with the coactivator AJUBA to cooperatively orchestrate transcriptional network activity in gastroesophageal adenocarcinoma; EHF expression is promoted by a core transcriptional regulatory circuitry (ELF3-KLF5-GATA6); KRAS signaling is a common downstream pathway of EHF and AJUBA. Co-immunoprecipitation (EHF-AJUBA interaction), ChIP, reporter assays, in vitro and in vivo functional experiments Acta pharmaceutica sinica. B Medium 38799645
2024 EHF forms liquid-like nuclear condensates (phase separation) that transcriptionally repress TERT and inflammatory factors (IL-6, CXCL12); reduction of TERT leads to telomere shortening and cellular senescence in PDAC without the senescence-associated secretory phenotype (SASP). Bilobetin promotes EHF phase separation. CRISPR/Cas9 library screening, phase separation assays, ChIP, telomere length assays, drug screening, in vivo experiments Cancer letters Medium 39710057
2024 Loss of Ehf in the mouse mammary gland impairs lobuloalveolar differentiation at late pregnancy, reduces milk gene/lipid levels, and causes accumulation of alveolar progenitor cells; Ehf deletion attenuates prolactin-induced alveolar differentiation in mammary organoids and increases tumor incidence in the MMTV-PyMT model. Conditional Ehf knockout mouse model, mammary organoids, in vivo tumor model, gene expression analysis Developmental cell High 38781975
2025 Loss of EHF in human iPSC-derived lung cells enhances CFTR activity, increases transepithelial electrical resistance, causes transcriptomic changes in basal cells, and reduces HIF-1α-mediated hypoxic response, indicating EHF controls multiple lung epithelial functions including ion channel regulation and hypoxia response. CRISPR EHF knockout in iPSC-derived lung cells, electrophysiology, RNA-seq, HIF-1α pathway analysis Disease models & mechanisms Medium 40590703
2022 Ehf plays a non-redundant role in salivary gland ductal cell differentiation; CRISPR-Cas9 disruption of the Ehf ETS domain causes decreased granular convoluted tubules and increased intercalated Sox9-positive ductal cell accumulation, with a pronounced sexual dimorphism in males. CRISPR-Cas9 Ehf ETS domain knockout mouse, histology, immunostaining Journal of dental research Medium 36348499
2006 ESE-3/EHF regulates DR-5 (death receptor 5) expression through direct binding to putative ETS sites on the DR-5 promoter; co-factors CBP and p300 are involved in ESE-3-mediated DR-5 upregulation. EMSA, luciferase reporter assay, co-factor interaction analysis Biochemical and biophysical research communications Medium 17027647
2016 ESE-3/EHF cooperates with pregnane X receptor (PXR) to transactivate the ABCB1 gene in intestinal epithelial cells; ESE-3 directly binds the DR4-containing distal enhancer module of ABCB1 as shown by ChIP, and this interaction is required for rifampicin-induced ABCB1 expression. ChIP, reporter assays with DR4 mutation, siRNA knockdown, RT-PCR Drug metabolism and pharmacokinetics High 27567379
2023 RRAD binds and regulates the subcellular localization of the transcription factor EHF in papillary thyroid cancer; EHF activates transcription of NEAT1_2, HK2, and PKM2, forming a NEAT1_2/RRAD/EHF positive feedback loop that facilitates aerobic glycolysis. Co-immunoprecipitation (RRAD-EHF), ChIP, luciferase reporter assays, RNA binding protein IP, subcellular fractionation Endocrinology Medium 37279586
2025 EHF in M2 tumor-associated macrophages promotes liver cancer cell metastasis by binding the KDM2B promoter and activating its transcription, which leads to increased IL-6 secretion. CUT-Tag, ChIP, luciferase assay, siRNA knockdown, co-culture migration/invasion assay, in vivo Cellular signalling Medium 39971220
2026 EHF regulates conventional dendritic cell maturation and immunosuppression after TLR7/8/9 stimulation by directly regulating Ccr7, Cd200, Cd274 (PD-L1), Irf4, and Rel expression, as shown by CUT&TAG; EHF-deficient DCs promote Th1/Th17-biased CD4+ T cell responses. Conditional DC-specific Ehf knockout mice, CUT&TAG, single-cell RNA-seq, T cell polarization assays, in vivo autoimmune/tumor models Nature communications High 41730908
2025 EHF in lung cancer cell-derived exosomes is transferred to macrophages and promotes M2 polarization by binding the RNF41 promoter and activating its transcription; inhibition of EHF/RNF41 axis suppresses tumor growth in vivo. ChIP, dual-luciferase reporter, exosome isolation and transfer assay, TEM, nanoparticle tracking, flow cytometry, in vivo xenograft Regenerative therapy Medium 41939996

Source papers

Stage 0 corpus · 77 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features. Cancer research 108 22505649
2018 ELF3, ELF5, EHF and SPDEF Transcription Factors in Tissue Homeostasis and Cancer. Molecules (Basel, Switzerland) 97 30200227
2000 ESE-3, a novel member of an epithelium-specific ets transcription factor subfamily, demonstrates different target gene specificity from ESE-1. The Journal of biological chemistry 96 10644770
2019 A novel miR-365-3p/EHF/keratin 16 axis promotes oral squamous cell carcinoma metastasis, cancer stemness and drug resistance via enhancing β5-integrin/c-met signaling pathway. Journal of experimental & clinical cancer research : CR 87 30782177
2001 The epithelium-specific ETS protein EHF/ESE-3 is a context-dependent transcriptional repressor downstream of MAPK signaling cascades. The Journal of biological chemistry 72 11259407
2016 Activation of the Lin28/let-7 Axis by Loss of ESE3/EHF Promotes a Tumorigenic and Stem-like Phenotype in Prostate Cancer. Cancer research 61 27197175
2008 Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells: potential roles in airway inflammation. Cell research 59 18475289
2007 Reduced expression and tumor suppressor function of the ETS transcription factor ESE-3 in prostate cancer. Oncogene 57 18037958
2017 Ets homologous factor (EHF) has critical roles in epithelial dysfunction in airway disease. The Journal of biological chemistry 54 28461336
2013 The Ets transcription factor EHF as a regulator of cornea epithelial cell identity. The Journal of biological chemistry 53 24142692
2016 ESE3 Inhibits Pancreatic Cancer Metastasis by Upregulating E-Cadherin. Cancer research 51 27923832
2021 ESE3/EHF, a promising target of rosiglitazone, suppresses pancreatic cancer stemness by downregulating CXCR4. Gut 41 33674341
2016 The ETS factor ESE3/EHF represses IL-6 preventing STAT3 activation and expansion of the prostate cancer stem-like compartment. Oncotarget 39 27732936
2002 Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung. American journal of respiratory cell and molecular biology 39 12444029
2024 Targeting ESE3/EHF With Nifurtimox Inhibits CXCR2+ Neutrophil Infiltration and Overcomes Pancreatic Cancer Resistance to Chemotherapy and Immunotherapy. Gastroenterology 38 38492894
2021 Pancreatic cancer cell-derived microRNA-155-5p-containing extracellular vesicles promote immune evasion by triggering EHF-dependent activation of Akt/NF-κB signaling pathway. International immunopharmacology 38 34482266
2015 Knockdown of EHF inhibited the proliferation, invasion and tumorigenesis of ovarian cancer cells. Molecular carcinogenesis 37 26258986
2011 A member of the ETS family, EHF, and the ATPase RUVBL1 inhibit p53-mediated apoptosis. EMBO reports 36 21617703
2001 Cow's milk-specific cellular and humoral immune responses and atopy skin symptoms in infants from atopic families fed a partially (pHF) or extensively (eHF) hydrolyzed infant formula. Allergy 29 11736743
2021 EHF suppresses cancer progression by inhibiting ETS1-mediated ZEB expression. Oncogenesis 27 33712555
2021 Activation of EHF via STAT3 phosphorylation by LMP2A in Epstein-Barr virus-positive gastric cancer. Cancer science 27 34014591
2013 The CF-modifying gene EHF promotes p.Phe508del-CFTR residual function by altering protein glycosylation and trafficking in epithelial cells. European journal of human genetics : EJHG 25 24105369
1999 Human chromosomal localization, tissue/tumor expression, and regulatory function of the ets family gene EHF. Biochemical and biophysical research communications 25 10527851
2015 The Transcription Factor Ehf Is Involved in TGF-β-Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells. Journal of immunology (Baltimore, Md. : 1950) 24 26297757
2019 The Edwardsiella piscicida Type III Effector EseJ Suppresses Expression of Type 1 Fimbriae, Leading to Decreased Bacterial Adherence to Host Cells. Infection and immunity 22 30988056
2020 EHF promotes colorectal carcinoma progression by activating TGF-β1 transcription and canonical TGF-β signaling. Cancer science 21 32372436
1998 Molecular cloning and expression of Ehf, a new member of the ets transcription factor/oncoprotein gene family. Biochemical and biophysical research communications 21 9600089
2005 Epithelial-specific transcription factor ESE-3 is involved in the development of monocyte-derived DCs. Blood 20 16380452
2022 Epithelial de-differentiation triggered by co-ordinate epigenetic inactivation of the EHF and CDX1 transcription factors drives colorectal cancer progression. Cell death and differentiation 18 35606410
2015 Abnormal Localization and Tumor Suppressor Function of Epithelial Tissue-Specific Transcription Factor ESE3 in Esophageal Squamous Cell Carcinoma. PloS one 18 25950810
2021 EHF is essential for epidermal and colonic epithelial homeostasis, and suppresses Apc-initiated colonic tumorigenesis. Development (Cambridge, England) 17 34180969
2017 Regulatory dynamics of 11p13 suggest a role for EHF in modifying CF lung disease severity. Nucleic acids research 17 28549169
2016 Increased expression of EHF contributes to thyroid tumorigenesis through transcriptionally regulating HER2 and HER3. Oncotarget 16 27517321
2007 ESE-3, an Ets family transcription factor, is up-regulated in cellular senescence. Cancer science 16 17627613
2024 Ehf and Fezf2 regulate late medullary thymic epithelial cell and thymic tuft cell development. Frontiers in immunology 15 38420512
2021 Loss of EHF facilitates the development of treatment-induced neuroendocrine prostate cancer. Cell death & disease 15 33414441
2020 Edwardsiella piscicida type III protein EseJ suppresses apoptosis through down regulating type 1 fimbriae, which stimulate the cleavage of caspase-8. Cellular microbiology 12 32068939
2019 Coordinate regulation of ELF5 and EHF at the chr11p13 CF modifier region. Journal of cellular and molecular medicine 12 31557407
2013 The SRC family tyrosine kinase HCK and the ETS family transcription factors SPIB and EHF regulate transcytosis across a human follicle-associated epithelium model. The Journal of biological chemistry 12 23439650
2021 EHF enhances malignancy by modulating AKT and MAPK/ERK signaling in non‑small cell lung cancer cells. Oncology reports 10 33907840
2022 The ETS Homologous Factor (EHF) Represents a Useful Immunohistochemical Marker for Predicting Prostate Cancer Metastasis. Diagnostics (Basel, Switzerland) 9 35453848
2022 Genetic Study of Elf5 and Ehf in the Mouse Salivary Gland. Journal of dental research 9 36348499
2023 NEAT1_2/RRAD/EHF Positive Feedback Loop Facilitates Aerobic Glycolysis in Papillary Thyroid Cancer Cells. Endocrinology 8 37279586
2012 Expression of ESE-3 isoforms in immunogenic and tolerogenic human monocyte-derived dendritic cells. PloS one 8 23185370
2005 Natural killer cell cytotoxic activity and c-Fos protein synthesis in rat hypothalamic cells after painful electric stimulation of the hind limbs and EHF irradiation of the skin. Medical science monitor : international medical journal of experimental and clinical research 8 16127352
2021 Ese-3 contributes to colon cancer progression by downregulating EHD2 and transactivating INPP4B. American journal of cancer research 7 33520362
2019 Proteasome inhibitor MG132 suppresses pancreatic ductal adenocarcinoma-cell migration by increasing ESE3 expression. Oncology letters 7 31897200
2014 Epithelium specific ETS transcription factor, ESE-3, of Protobothrops flavoviridis snake venom gland transactivates the promoters of venom phospholipase A2 isozyme genes. Toxicon : official journal of the International Society on Toxinology 7 25449102
2006 ESE-3 transcription factor is involved in the expression of death receptor (DR)-5 through putative Ets sites. Biochemical and biophysical research communications 7 17027647
2025 BRAF-induced EHF Expression Affects TERT in Aggressive Papillary Thyroid Cancer. The Journal of clinical endocrinology and metabolism 6 39183149
2016 Involvement of ESE-3, epithelial-specific ETS factor family member 3, in transactivation of the ABCB1 gene via pregnane X receptor in intestine-derived LS180 cells but not in liver-derived HepG2 cells. Drug metabolism and pharmacokinetics 6 27567379
2024 Transcription factor EHF drives cholangiocarcinoma development through transcriptional activation of glioma-associated oncogene homolog 1 and chemokine CCL2. MedComm 5 38741887
2024 Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma. Acta pharmaceutica Sinica. B 5 38799645
2014 Activation of peroxisome proliferator-activated receptor gamma leads to upregulation of ESE-3 expression in human monocyte-derived dendritic cells. Scandinavian journal of immunology 5 24219556
1994 [The mechanism of synchronizing yeast cell cultures with EHF-radiation]. Biofizika 5 8043637
2024 Cpeb4-mediated Dclk2 promotes neuronal pyroptosis induced by chronic cerebral ischemia through phosphorylation of Ehf. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 4 38513137
2024 Ehf controls mammary alveolar lineage differentiation and is a putative suppressor of breast tumorigenesis. Developmental cell 4 38781975
2017 miR‑206 inhibits cancer initiating cells by targeting EHF in gastric cancer. Oncology reports 4 28714026
2014 Polymorphisms of EHF-ELF5 genomic region and its association with pediatric asthma in the Taiwanese population. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 4 25648666
2007 Responses of hypothalamic orexin-containing neurons to cyclophosphamide, EHF-irradiation of the skin, and their combination in rats. Pathophysiology : the official journal of the International Society for Pathophysiology 4 17881193
2024 The nuclear condensates of ESE3/EHF induce cellular senescence without the associated inflammatory secretory phenotype in pancreatic ductal adenocarcinoma. Cancer letters 3 39710057
2021 Ese-3 Inhibits the Proliferation, Migration, and Invasion of HaCaT Cells by Downregulating PSIP1 and NUCKS1. Annals of clinical and laboratory science 3 34452885
2025 EHF promotes liver cancer progression by meditating IL-6 secretion through transcription regulation of KDM2B in TAMs. Cellular signalling 2 39971220
2025 LncRNA LINC01026 Is Overexpressed in Psoriasis and Enhances Keratinocyte Cell Cycle Progression by Regulating the Ets Homologous Factor (EHF). Journal of cellular and molecular medicine 2 40670887
2008 Morphometric analysis of hypothalamic cells showing c-Fos proteins after movement restriction and EHF-irradiation. Pathophysiology : the official journal of the International Society for Pathophysiology 2 18313906
1995 [Significance of the functional state of blood phagocytes in the choice of optimal regime of EHF therapy of patients with pulmonary tuberculosis]. Problemy tuberkuleza 2 8524760
2024 TMB Signature-Related RCAN2 Promotes Apoptosis by Upregulating EHF/DR5 Pathway in Hepatocellular Carcinoma. Frontiers in bioscience (Landmark edition) 1 39082336
2026 The transcription factor EHF promotes the maturation and immunosuppression of conventional dendritic cells. Nature communications 0 41730908
2026 Lung cancer cell-derived exosomal EHF drives M2 macrophage polarization via transcriptional activation of RNF41 to promote tumor progression. Regenerative therapy 0 41939996
2025 Evaluating Type III Secretion System Genes (escE, esaE and eseJ) of Edwardsiella piscicida for Virulence in Japanese Flounder (Paralichthys olivaceus). Journal of fish diseases 0 40485376
2025 An in vitro model of the epithelial airway reveals a key function for EHF in lung homeostasis and disease. Disease models & mechanisms 0 40590703
2025 T3SS effector EseJ in Edwardsiella piscicida inhibits PANoptosis in macrophages. Communications biology 0 41044169
2024 Codon Bias of the DDR1 Gene and Transcription Factor EHF in Multiple Species. International journal of molecular sciences 0 39409024
2023 [Retracted] miR‑206 inhibits cancer initiating cells by targeting EHF in gastric cancer. Oncology reports 0 37772393
2007 [Expression of c-Fos gene in the rat hypothalamus upon electric painful stimulation and EHF irradiation of the skin]. Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova 0 17598468
2005 [Study of the systemic-organ blood circulation in acute period of the multiple trauma based on water-electrolytic metabolism and its correction with EHF-therapy]. Likars'ka sprava 0 16025675
1995 [The ultrastructural characteristics of the duodenal mucosa in peptic ulcer patients undergoing treatment with EHF-range electromagnetic radiation]. Likars'ka sprava 0 8630825