Affinage

ESRP1

Epithelial splicing regulatory protein 1 · UniProt Q6NXG1

Length
681 aa
Mass
75.6 kDa
Annotated
2026-06-09
70 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ESRP1 is an epithelial cell-type-specific RNA-binding protein that coordinates a global epithelial post-transcriptional program, regulating >100 alternative splicing events in transcripts governing actin cytoskeleton organization, cell-cell adhesion, polarity, and migration (PMID:19285943, PMID:19829082). Reciprocal gain- and loss-of-function established its defining activity as a regulator of mutually exclusive FGFR2 IIIb/IIIc splicing and of CD44, CTNND1, and ENAH/MENA isoform choice (PMID:19285943, PMID:22673910). eCLIP in epidermis showed that ESRP1 acts through direct, position-dependent binding that promotes exon inclusion or skipping, and also binds widely to 3′ and 5′ UTRs, extending its role beyond splicing to mRNA stability control (PMID:36238894); a crystal structure of its qRRM2 domain bound to GGU motifs embedded in aromatic clamp-like pockets provides the molecular basis for sequence-specific recognition (PMID:38015468). Through its UTR-binding activity ESRP1 stabilizes target mRNAs such as PHGDH and destabilizes others including cyclin A2, and it drives back-splicing of circular RNAs (circDOCK1, circPTPN12) by detaining splicing at GGU-rich introns (PMID:38015468, PMID:31362365, PMID:36925195, PMID:38992675). The splicing program it controls converges on epithelial morphogenesis: Esrp1 knockout mice develop fully penetrant cleft lip and palate, skin barrier failure, hearing loss through aberrant Fgfr2 splicing that mis-routes FGF9 signaling, and oocyte meiotic spindle defects (PMID:26371508, PMID:29107558, PMID:33318146), and CTNND1 (p120-catenin) is a key downstream effector whose overexpression rescues epithelial morphogenesis in esrp1/2 mutants (PMID:39179789). ESRP1 is transcriptionally repressed by Snail/SLUG and RBFOX2 during EMT and induced by E2F1 together with TET3-mediated promoter hydroxymethylation (PMID:33089214, PMID:34362878, PMID:29131012), and its protein level is further controlled by ISGylation (PMID:32641707). Direct evidence links ESRP1 mutations to human sensorineural hearing loss via disrupted target splicing (PMID:29107558).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2009 High

    Established ESRP1's foundational identity by showing an epithelial-specific RNA-binding protein directly controls the FGFR2 IIIb/IIIc splicing switch, defining the molecular determinant of an epithelial splicing program.

    Evidence cDNA expression screen with reciprocal ectopic expression and RNAi in epithelial/mesenchymal cell lines, RT-PCR isoform analysis

    PMID:19285943

    Open questions at the time
    • Direct RNA binding sites not yet mapped
    • Did not distinguish direct splicing targets from indirect effects
  2. 2009 High

    Defined the scope of ESRP1 as a master splicing regulator by genome-wide profiling, showing it controls a coordinated program of >100 events in cytoskeleton, adhesion, polarity, and migration genes.

    Evidence Exon ST1.0 splicing array after ESRP1/2 RNAi with RT-PCR validation of 38 targets

    PMID:19829082

    Open questions at the time
    • Array does not resolve direct vs indirect targets
    • No binding map to assign mechanism per exon
  3. 2012 High

    Connected ESRP1 splicing activity to disease phenotype by showing CD44v/CD44s isoform control governs xCT surface stability and metastatic lung colonization.

    Evidence RNAi knockdown, RT-PCR, orthotopic transplantation mouse model

    PMID:22673910

    Open questions at the time
    • Mechanism of CD44v stabilizing xCT not fully resolved
    • Generalizability beyond breast cancer model unaddressed
  4. 2013 Medium

    Revealed ESRP1 functions beyond splicing as a translational regulator and nuclear-speckle partner, binding Oct4/Sox2 mRNAs to limit pluripotency and associating with PNN.

    Evidence RIP and polysome fractionation in ES cells; co-IP and co-localization with PNN in corneal epithelium

    PMID:23299472 PMID:24015231

    Open questions at the time
    • PNN co-IP not reciprocally validated for direct contact
    • Translational repression mechanism on Oct4/Sox2 not defined
  5. 2015 High

    Demonstrated in vivo essentiality by showing germline Esrp1 loss causes fully penetrant cleft lip/palate and epidermal Esrp loss disrupts skin barrier, establishing ESRP-dependent splicing as required for epithelial organogenesis.

    Evidence Conditional and germline knockout mice with RNA-Seq of epidermis and phenotypic analysis

    PMID:26371508

    Open questions at the time
    • Which specific splicing changes drive each phenotype not isolated
    • Esrp1 vs Esrp2 contributions partially redundant
  6. 2017 High

    Linked ESRP1 to human Mendelian disease and resolved a signaling epistasis, showing mutations cause sensorineural hearing loss via aberrant Fgfr2 splicing that mis-routes FGF9 ligand usage.

    Evidence Whole-exome sequencing of patients, iPSC allele repair, Esrp1-KO cochlear RNA-Seq, Fgf9 genetic rescue

    PMID:29107558

    Open questions at the time
    • Full target set underlying stria vascularis defect not enumerated
    • Penetrance and allelic spectrum in humans limited
  7. 2017 Medium

    Showed ESRP1 itself is autoregulated and spatially partitioned, with exon 12 alternative splicing producing nuclear versus cytoplasmic isoforms in a conserved manner.

    Evidence RT-PCR isoform characterization, subcellular fractionation, microscopy, Drosophila ortholog comparison

    PMID:28634384

    Open questions at the time
    • Functional consequence of isoform localization difference not tested
    • Regulation of exon 12 choice unknown
  8. 2018 Medium

    Placed ESRP1 within a competitive splicing-factor network by showing it acts antagonistically to hnRNPM at shared GU-rich cis-elements, and is transcriptionally silenced by Snail during EMT.

    Evidence Comparative knockdown splicing analysis with motif enrichment; ChIP and reporter assays for Snail at ESRP1 promoter

    PMID:29131012 PMID:29431637 PMID:30042172

    Open questions at the time
    • Direct competition at individual exons not biochemically reconstituted
    • Snail-ESRP1 axis context-dependence across tissues unclear
  9. 2020 Medium

    Expanded the transcriptional and post-translational control of ESRP1, showing SLUG/RBFOX2 repress it under hypoxia while ISGylation stabilizes its protein in a CREB-ISG15 feedback loop.

    Evidence ChIP, RNAi, co-IP for ISGylation, reporter assays in cancer cell lines

    PMID:32641707 PMID:33089214

    Open questions at the time
    • ISGylation site on ESRP1 not mapped
    • Crosstalk between transcriptional and ISGylation control not integrated
  10. 2021 Medium

    Established the E2F1/TET3 hydroxymethylation axis as the inductive arm of ESRP1 regulation and extended ESRP1 phenotypes to oocyte meiosis through splicing of microtubule cytoskeletal genes.

    Evidence ChIP, bisulfite sequencing, reporter assays; Esrp1 conditional KO mice with single-cell RNA-seq of oocytes

    PMID:33318146 PMID:34362878

    Open questions at the time
    • Direct splicing targets causing spindle defects not validated individually
    • TET3-E2F1 mechanism shown in one cancer context
  11. 2022 High

    Provided the first in vivo direct binding map and showed ESRP1 binds UTRs as well as splice sites, mechanistically unifying its splicing and mRNA-fate functions.

    Evidence eCLIP in mouse epidermis integrated with Esrp1/2-null RNA-Seq

    PMID:36238894

    Open questions at the time
    • UTR-binding consequences (stability/translation) not assayed transcriptome-wide
    • Position rules derived from epidermis only
  12. 2024 High

    Delivered the structural basis of sequence recognition and a novel function in circRNA biogenesis, showing the qRRM2 domain clamps GGU motifs to detain splicing and drive back-splicing of circDOCK1.

    Evidence HITS-CLIP, X-ray crystallography of qRRM2-RNA complex, CRISPR deletions, motility assays

    PMID:38015468

    Open questions at the time
    • Generality of GGU-clamp recognition across all targets not demonstrated
    • Contribution of the other two RRMs unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ESRP1's position-dependent binding code, UTR-mediated stability control, and circRNA biogenesis activity are integrated into a single tissue-specific regulatory logic remains unresolved.
  • No unified model linking splice-site vs UTR binding outcomes
  • Roles of the three RRMs and isoform localization in target selection undefined
  • Lactylation and other PTMs reported only at Low confidence

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0140098 catalytic activity, acting on RNA 4 GO:0045182 translation regulator activity 1
Localization
GO:0005654 nucleoplasm 2 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-8953854 Metabolism of RNA 4
Partners
HNRNPMPNNRBFOX2RBPMS2

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 ESRP1 (and its paralog ESRP2) are epithelial cell-type-specific RNA-binding proteins that directly regulate mutually exclusive splicing of FGFR2 exons IIIb and IIIc: ectopic expression of ESRP1 in mesenchymal cells switches endogenous FGFR2 splicing to the epithelial IIIb isoform, while RNAi knockdown of both ESRPs in epithelial cells switches splicing to the mesenchymal IIIc isoform. ESRP1 also regulates splicing of CD44, CTNND1 (p120-catenin), and ENAH (hMena). cDNA expression screen, ectopic expression in cell lines, RNAi knockdown, RT-PCR isoform analysis Molecular cell High 19285943
2009 Genome-wide profiling via splicing-sensitive exon arrays following RNAi knockdown of ESRP1/2 in human epithelial cells identified >100 ESRP-regulated splicing events (38 independently validated by RT-PCR), encompassing cassette exons and alternative 3′ terminal exons; regulated transcripts encode proteins involved in actin cytoskeleton organization, cell-cell adhesion, cell polarity, and cell migration. Affymetrix Exon ST1.0 array after RNAi knockdown, RT-PCR validation RNA biology High 19829082
2012 ESRP1 controls alternative splicing of CD44 pre-mRNA, promoting expression of CD44 variant isoforms (CD44v) over the standard isoform (CD44s); knockdown of ESRP1 in CD44v+ breast cancer cells causes an isoform switch from CD44v to CD44s, leading to reduced cell-surface xCT (cystine transporter) and suppressed lung colonization. RNAi knockdown, RT-PCR isoform analysis, orthotopic transplantation mouse model Nature communications High 22673910
2014 ESRP1 suppresses cancer cell motility through regulation of actin cytoskeleton dynamics via Rac1b: knockdown of ESRP1 (but not ESRP2) in head and neck carcinoma cells induces Rac1b expression and alters actin cytoskeleton dynamics, promoting a motile phenotype. RNAi knockdown, cell motility assays, western blot for Rac1b The Journal of biological chemistry Medium 25143390
2015 Esrp1 knockout mice develop fully penetrant bilateral cleft lip and palate; combined Esrp1/Esrp2 double knockout produces widespread developmental defects. Epidermal deletion of Esrps disrupts skin barrier function, demonstrating that Esrp1-mediated alternative splicing is essential for epithelial cell function in vivo. Conditional and germline knockout mice, RNA-Seq of epidermis, phenotypic analysis eLife High 26371508
2017 ESRP1 mutations in humans cause sensorineural hearing loss (SNHL) by disrupting alternative splicing of target genes; in Esrp1−/− mouse embryos, aberrant splicing of Fgfr2 blocks stria vascularis formation due to erroneous FGF ligand usage, which was corrected by reducing Fgf9 gene dosage — establishing a genetic epistasis between Fgfr2 splicing and Fgf9 signaling downstream of ESRP1. Whole-exome sequencing of SNHL patients, iPSC allele repair, Esrp1-KO mouse cochlear analysis, RNA-Seq, Fgf9 genetic rescue Developmental cell High 29107558
2017 ESRP1 regulates alternative splicing of GPR137 to produce isoforms that differentially activate the Wnt signaling pathway; reduced ESRP1 function impairs intestinal barrier integrity and alters colorectal cancer development through GPR137 isoform switching. Mouse genetic model (reduced Esrp1 function), Wnt pathway reporter assays, RT-PCR isoform analysis eLife Medium 28975893
2017 Alternative splicing of Esrp1 exon 12 via competing 5′ splice sites produces protein isoforms with distinct nuclear versus cytoplasmic localization; a specific peptide encoded by exon 12 is sufficient to confer nuclear localization. This differential subcellular localization is phylogenetically conserved (also found in Drosophila fusilli, the Esrp1 ortholog). RT-PCR isoform characterization, subcellular fractionation, fluorescence microscopy, Drosophila ortholog analysis Scientific reports Medium 28634384
2013 ESRP1 protein physically associates with PNN (Pinin) in nuclear speckles of corneal epithelial cells (co-immunoprecipitation), and both regulate overlapping but distinct sets of alternative splicing events in corneal epithelium. Co-immunoprecipitation, deconvolution microscopy co-localization, genome-wide splicing array after knockdown Investigative ophthalmology & visual science Medium 23299472
2013 ESRP1 binds to Oct4 and Sox2 mRNAs in mouse embryonic stem cells and decreases their polysomal loading (translational repression), thereby acting as a physiological regulator of pluripotency; Esrp1 knockdown increases Oct4, Nanog, and Sox2 expression and enhances self-renewal. RNA immunoprecipitation (RIP) for Oct4/Sox2 mRNA binding, polysome fractionation, RNAi knockdown, in vitro/in vivo differentiation assays PloS one Medium 24015231
2019 ESRP1 knockdown in tamoxifen-resistant breast cancer cells affects lipid metabolism and oxidoreductase processes, reducing expression of fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), and phosphoglycerate dehydrogenase (PHGDH), and increases basal and spare mitochondrial respiration capacity. RNAi knockdown, western blot, RT-qPCR, Seahorse metabolic flux analysis EMBO reports Medium 30665944
2018 hnRNPM and ESRP1 co-regulate a set of cassette exon splicing events in an antagonistic (discordant) manner; motif enrichment near co-regulated exons identifies GU-rich motifs downstream of hnRNPM-repressed/ESRP1-enhanced exons, supporting a model of competitive binding to cis-regulatory elements. Comparative splicing analysis of hnRNPM and ESRP1 knockdown datasets, motif enrichment analysis, EMT correlation RNA (New York, N.Y.) Medium 30042172
2020 Transcriptional repression of ESRP1 under hypoxia is mediated by SLUG (downstream of TGF-β signaling) and by RBFOX2, which transcriptionally represses ESRP1 while interacting with SLUG; hypoxia-driven ESRP1 depletion causes skipping of hMENA exon 11a, producing a pro-metastatic hMENAΔ11a isoform. qRT-PCR, western blot, RNAi knockdown, chromatin immunoprecipitation for SLUG binding to ESRP1 promoter, RT-PCR isoform analysis NAR cancer Medium 33089214
2021 E2F1 and CpG hydroxymethylation (mediated by TET3) at the E2F1 binding motif in the ESRP1 promoter conjointly induce ESRP1 expression in breast carcinoma; under hypoxia, reduced TET3 activity causes loss of hydroxymethylation and gain of methylation at these CpG sites, preventing E2F1 binding and reducing ESRP1 transcription. ChIP, dual luciferase reporter, bisulfite sequencing, western blot, RNAi knockdown Oncogenesis Medium 34362878
2020 ESRP1 upregulates ISG15 expression through CREB (with CREB enriched at the ISG15 promoter), and in turn ISG15 promotes ISGylation of ESRP1 protein, slowing its degradation and forming a positive feedback loop that jointly suppresses EMT in lung adenocarcinoma. Co-immunoprecipitation for ISGylation, chromatin immunoprecipitation for CREB at ISG15 promoter, dual luciferase reporter, western blot Cell death & disease Medium 32641707
2021 ESRP1 regulates alternative splicing of CARM1 pre-mRNA to produce two transcripts (CARM1FL and CARM1ΔE15); the resulting CARM1 isoform ratio controls arginine methylation of Smad7, modulating TGF-β/Smad pathway activation and thereby influencing chemoresistance in small cell lung cancer. mRNA transcriptome sequencing, RT-PCR isoform analysis, overexpression/knockdown, western blot for Smad7 methylation Aging Medium 33495408
2021 Loss of ESRP1 in mouse oocytes disrupts alternative splicing of maternal mRNA transcripts (528 aberrant AS events identified by single-cell RNA-seq), particularly in microtubule cytoskeletal genes including Rac1, Kif2c, Kif23, Ndel1, and Bora, leading to abnormal spindle organization, blocked first polar body extrusion, and female infertility. Esrp1 conditional knockout mice, single-cell RNA-seq, spindle assembly checkpoint analysis, oocyte meiosis assays Development (Cambridge, England) Medium 33318146
2022 eCLIP mapping of ESRP1 binding sites in mouse epidermis revealed that ESRP1 functions in splicing through direct, position-dependent RNA binding to promote exon inclusion or skipping, and also binds widely to 3′ and 5′ UTRs of epithelial genes, indicating post-transcriptional regulatory functions beyond splicing. Enhanced CLIP-seq (eCLIP) in mouse epidermis, RNA-Seq of Esrp1/2-null epidermis, integration of binding and splicing data iScience High 36238894
2022 ESRP1 regulates isoform switching of LRRFIP2 between epithelial (variant 2) and mesenchymal (variant 3) isoforms; the epithelial LRRFIP2 isoform inhibits oncogenic CARM1 function through direct protein–protein interaction, and CRISPR-mediated deletion of LRRFIP2 exon 7 causes isoform switch and suppresses liver metastasis of gastric cancer cells. Ectopic expression, CRISPR/Cas9 exon deletion, liver metastasis mouse model, co-immunoprecipitation for LRRFIP2-CARM1 interaction Nature communications High 36307405
2024 ESRP1 controls biogenesis of the large circRNA circDOCK1(2-27) by binding GGU-containing repeat sequences in intron 1 of DOCK1 pre-mRNA, detaining splicing to enable back-splicing to exon 27. X-ray crystal structure of RNA-bound ESRP1 qRRM2 domain shows GGU motifs embedded in clamp-like aromatic pockets. CircDOCK1(2-27) represses cell motility both by diverting transcripts from DOCK1 mRNA production and by direct inhibition of migration. HITS-CLIP, CRISPR-mediated deletions, BioID proximity biotinylation, X-ray crystallography of qRRM2-RNA complex, cell motility assays Nucleic acids research High 38015468
2019 ESRP1 overexpression in CRC cells enhances FGFR1/2 signaling and Akt activation in anchorage-independent conditions, and promotes macrometastasis formation in mouse livers, establishing a pro-oncogenic role for ESRP1 in colorectal cancer through enhanced growth factor receptor signaling. Gain- and loss-of-function in CRC cell lines, mouse liver metastasis model, western blot for FGFR/Akt signaling Oncotarget Medium 28052020
2019 ESRP1 binds to the GGUGGU sequence in the 3′UTR of cyclin A2 mRNA, decreasing its stability; ESRP1 overexpression increases CDC20 expression (promoting cyclin A2 protein degradation) and induces G1-phase cell cycle arrest in cervical cancer cells. RNA immunoprecipitation, mRNA stability assay, overexpression, cell cycle analysis by flow cytometry, western blot International journal of molecular sciences Medium 31362365
2023 ESRP1 promotes exon 11 alternative splicing of CLSTN1 pre-mRNA; the resulting short CLSTN1 isoform stabilizes the E-cadherin/β-catenin complex and promotes β-catenin ubiquitination and degradation, thereby inhibiting gastric cancer cell migration and invasion. RNAi knockdown, overexpression, RT-PCR isoform analysis, co-immunoprecipitation, ubiquitination assay, in vitro/in vivo invasion assays Cell death discovery Medium 38114495
2016 Esrp1 overexpression in chicken stomach smooth muscle cells (SMCs) impairs SMC differentiation and switches FGFR2 splicing to the IIIb isoform; Esrp1 physically interacts with the RNA-binding protein RBPMS2 and RBPMS2-mediated SMC dedifferentiation requires Esrp1. Gain-of-function in chicken embryos, co-immunoprecipitation for ESRP1-RBPMS2 interaction, SMC differentiation assays, RT-PCR FGFR2 isoform analysis Developmental biology Medium 27108394
2020 Full-length APC expression in SW480 colorectal cancer cells increases ESRP1 expression, and ESRP1 depletion in SW480+APC cells reverts p120-catenin isoform switching (from isoform 3A back to isoform 1A) and reduces cell-cell adhesion, placing ESRP1 downstream of APC in the regulation of p120-catenin splicing and adhesion. APC re-expression, ESRP1 knockdown, RT-PCR p120-catenin isoform analysis, cell-cell adhesion assay Molecular biology of the cell Medium 33237836
2020 Irf6 regulates the expression of esrp1 in zebrafish periderm and orofacial epithelium; genetic disruption of irf6 and esrp1/2 in zebrafish causes cleft of the anterior neurocranium through impaired chondrogenesis (not neural crest cell migration defects), and Irf6 heterozygosity reduces cleft severity in Esrp1/2 mutants, demonstrating genetic interaction. Zebrafish genetic mutants, compound mouse mutants (Irf6;Esrp1;Esrp2), cranial neural crest lineage tracing, in situ hybridization Development (Cambridge, England) Medium 33234718
2020 Cleft lip in Esrp1 knockout mice is associated with altered epithelial-mesenchymal crosstalk; transcriptomic analysis of ectoderm and mesenchyme in Esrp1 embryos identified altered expression of genes in multiple signaling pathways (including those previously implicated in cleft lip/palate). Esrp1 KO mouse models, transcriptomic analysis of separated ectoderm and mesenchyme, histological analysis Development (Cambridge, England) Medium 32253237
2023 Decreased ESRP1 expression reduces MENA11a isoform expression by altering MENA alternative splicing; matrix stiffness decreases ESRP1 expression, triggering this splicing switch, which enhances cancer cell contractility via focal adhesion kinase activity and promotes intravasation. In vitro hydrogel stiffness systems, mouse model, western blot and RT-PCR, ESRP1 knockdown, intravasation assay Cell reports Medium 37027295
2023 ESRP1 binds to PHGDH mRNA at its 5′UTR and increases PHGDH mRNA stability in tamoxifen-resistant breast cancer cells; ESRP1 knockdown significantly decreases PHGDH mRNA stability in resistant cells. RNA-binding protein immunoprecipitation followed by microarray (RIP-Chip), immunoprecipitation-mass spectrometry, RNA EMSA, RIP-qRT-PCR, mRNA stability assay Laboratory investigation Medium 36925195
2018 Snail transcription factor directly represses ESRP1 transcription by binding to the ESRP1 promoter in epithelial ovarian cancer cells, establishing ESRP1 as a downstream transcriptional target of Snail during EMT. Chromatin immunoprecipitation (ChIP) for Snail at ESRP1 promoter, luciferase reporter, RNAi Cellular physiology and biochemistry Medium 29131012
2018 In non-small cell lung cancer, Snail-mediated silencing of ESRP1 is required for anchorage-independent growth and metastatic behavior; ESRP1 loss is a critical event in Snail-dependent malignant transformation of pulmonary epithelial cells, acting in an ALDH+CD44+CD24− stem cell subset. RNAi knockdown/rescue, anchorage-independent growth assay, in vivo primary tumor and metastasis models, FACS for stem cell markers Cancer research Medium 29431637
2024 ESRP1 binds to pre-PTPN12 RNA and promotes the biogenesis of circPTPN12; circPTPN12 interacts with the PDZ domain of PDLIM2 and promotes PDLIM2-mediated ubiquitination of NF-κB p65, placing ESRP1 upstream of circPTPN12 in a circRNA biogenesis and NF-κB suppression axis in hepatocellular carcinoma. RNA immunoprecipitation, biotin-coupled probe pull-down, FISH, RNA sequencing, in vitro/in vivo functional assays Molecular cancer Medium 38992675
2025 In zebrafish, Esrp1 and Esrp2 directly bind tmc1 and tmc2a mRNAs in sensory hair cells and regulate their stability; loss of esrp1/2 reduces tmc1/2a mRNA levels and impairs mechano-electrical transduction (MET) function of hair cells. Esrp1/2 double knockout zebrafish, RNA-sequencing, RNA binding assay for tmc1/tmc2a mRNA, electrophysiological MET assay The Journal of neuroscience Medium 40086870
2024 Overexpression of CTNND1 (p120-catenin) is sufficient to rescue morphogenesis of epithelial-derived structures in esrp1/2 zebrafish mutants, placing Ctnnd1 as a key downstream effector of Esrp1-regulated splicing in palatogenesis. esrp1/2 zebrafish mutants, CTNND1 overexpression rescue experiments, RT-PCR for Ctnnd1 isoforms Communications biology Medium 39179789
2026 Lactylation of ESRP1 at lysine 43 (K43) stabilizes ESRP1 protein; glycolytic lactate promotes this modification. ESRP1 regulates biogenesis of circPHGDH, and circPHGDH knockdown suppresses ESRP1 lactylation, forming a positive feedback loop driving prostate cancer progression. RNA immunoprecipitation, immunoprecipitation, western blot for lactylation, site-directed mutagenesis (K43), luciferase reporter, RNA pull-down Experimental & molecular medicine Low 41760734
2025 ESRP1 interacts with DHCR7 protein and upregulates DHCR7 expression, enhancing ferroptosis susceptibility in diffuse-type gastric cancer cells; both in vitro and in vivo models confirm ESRP1 inhibits DGC malignant progression through this mechanism. Co-immunoprecipitation for ESRP1-DHCR7 interaction, overexpression/knockdown, xenograft mouse model, ferroptosis assays Journal of experimental & clinical cancer research Low 40528239
2025 ESRP1 overexpression in alveolar epithelial cells promotes EMT via activation of the Epac-Rap1a signaling axis; Co-IP demonstrated direct interaction between ESRP1, Epac, and Rap1a. Silencing of Epac or Rap1a did not alter ESRP1 expression, confirming ESRP1 is upstream. Single-cell RNA-seq, co-immunoprecipitation, lentiviral overexpression, siRNA knockdown, TGF-β1-induced EMT model Frontiers in medicine Low 41728622

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing. Molecular cell 484 19285943
2012 Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell. Nature communications 320 22673910
2009 The epithelial splicing factors ESRP1 and ESRP2 positively and negatively regulate diverse types of alternative splicing events. RNA biology 178 19829082
2014 Epithelial splicing regulatory proteins 1 (ESRP1) and 2 (ESRP2) suppress cancer cell motility via different mechanisms. The Journal of biological chemistry 134 25143390
2015 The splicing regulators Esrp1 and Esrp2 direct an epithelial splicing program essential for mammalian development. eLife 129 26371508
2019 Splicing factor ESRP1 controls ER-positive breast cancer by altering metabolic pathways. EMBO reports 67 30665944
2018 Interconnected feedback loops among ESRP1, HAS2, and CD44 regulate epithelial-mesenchymal plasticity in cancer. APL bioengineering 65 31069317
2018 Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT. RNA (New York, N.Y.) 63 30042172
2016 Altered Expression and Splicing of ESRP1 in Malignant Melanoma Correlates with Epithelial-Mesenchymal Status and Tumor-Associated Immune Cytolytic Activity. Cancer immunology research 56 27045022
2017 The RNA-binding protein ESRP1 promotes human colorectal cancer progression. Oncotarget 54 28052020
2017 Snail Driving Alternative Splicing of CD44 by ESRP1 Enhances Invasion and Migration in Epithelial Ovarian Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 53 29131012
2017 ESRP1 is overexpressed in ovarian cancer and promotes switching from mesenchymal to epithelial phenotype in ovarian cancer cells. Oncogenesis 52 28991261
2020 Hypoxia-induced TGF-β-RBFOX2-ESRP1 axis regulates human MENA alternative splicing and promotes EMT in breast cancer. NAR cancer 49 33089214
2021 Circ_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis. Genes 47 34828307
2017 ESRP1 Mutations Cause Hearing Loss due to Defects in Alternative Splicing that Disrupt Cochlear Development. Developmental cell 46 29107558
2021 Circ-NOLC1 promotes epithelial ovarian cancer tumorigenesis and progression by binding ESRP1 and modulating CDK1 and RhoA expression. Cell death discovery 43 33483472
2020 Cleft lip and cleft palate in Esrp1 knockout mice is associated with alterations in epithelial-mesenchymal crosstalk. Development (Cambridge, England) 37 32253237
2013 The RNA binding protein ESRP1 fine-tunes the expression of pluripotency-related factors in mouse embryonic stem cells. PloS one 36 24015231
2016 Epigenetic regulation of ZEB1-RAB25/ESRP1 axis plays a critical role in phenylbutyrate treatment-resistant breast cancer. Oncotarget 33 26646320
2021 Loss of ESRP1 blocks mouse oocyte development and leads to female infertility. Development (Cambridge, England) 32 33318146
2020 Bleomycin induces epithelial-to-mesenchymal transition via bFGF/PI3K/ESRP1 signaling in pulmonary fibrosis. Bioscience reports 32 31868203
2017 Dual Roles for Epithelial Splicing Regulatory Proteins 1 (ESRP1) and 2 (ESRP2) in Cancer Progression. Advances in experimental medicine and biology 30 27401076
2021 ESRP1 regulates alternative splicing of CARM1 to sensitize small cell lung cancer cells to chemotherapy by inhibiting TGF-β/Smad signaling. Aging 29 33495408
2024 ESRP1-mediated biogenesis of circPTPN12 inhibits hepatocellular carcinoma progression by PDLIM2/ NF-κB pathway. Molecular cancer 28 38992675
2020 High expression of ESRP1 regulated by circ-0005585 promotes cell colonization in ovarian cancer. Cancer cell international 28 32467669
2022 ESRP1-regulated isoform switching of LRRFIP2 determines metastasis of gastric cancer. Nature communications 26 36307405
2019 ESRP1 Induces Cervical Cancer Cell G1-Phase Arrest Via Regulating Cyclin A2 mRNA Stability. International journal of molecular sciences 26 31362365
2020 An Irf6-Esrp1/2 regulatory axis controls midface morphogenesis in vertebrates. Development (Cambridge, England) 25 33234718
2023 Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA. Cell reports 24 37027295
2021 E2F1 and epigenetic modifiers orchestrate breast cancer progression by regulating oxygen-dependent ESRP1 expression. Oncogenesis 24 34362878
2020 ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression. Cell death & disease 24 32641707
2017 The ESRP1-GPR137 axis contributes to intestinal pathogenesis. eLife 24 28975893
2013 During embryogenesis, esrp1 expression is restricted to a subset of epithelial cells and is associated with splicing of a number of developmentally important genes. Developmental dynamics : an official publication of the American Association of Anatomists 24 23233200
2024 ESRP1 controls biogenesis and function of a large abundant multiexon circRNA. Nucleic acids research 23 38015468
2023 ESRP1-driven alternative splicing of CLSTN1 inhibits the metastasis of gastric cancer. Cell death discovery 20 38114495
2020 Emerging Multi-cancer Regulatory Role of ESRP1: Orchestration of Alternative Splicing to Control EMT. Current cancer drug targets 20 32564755
2017 Alternative splicing regulates distinct subcellular localization of Epithelial splicing regulatory protein 1 (Esrp1) isoforms. Scientific reports 20 28634384
2020 APC regulation of ESRP1 and p120-catenin isoforms in colorectal cancer cells. Molecular biology of the cell 18 33237836
2019 Integrated Analysis of Structural Variation and RNA Expression of FGFR2 and Its Splicing Modulator ESRP1 Highlight the ESRP1amp-FGFR2norm-FGFR2-IIIchigh Axis in Diffuse Gastric Cancer. Cancers 18 31881796
2016 Ablation of the epithelial-specific splicing factor Esrp1 results in ureteric branching defects and reduced nephron number. Developmental dynamics : an official publication of the American Association of Anatomists 17 27404344
2013 Transcriptomic analysis of PNN- and ESRP1-regulated alternative pre-mRNA splicing in human corneal epithelial cells. Investigative ophthalmology & visual science 17 23299472
2020 Proteomics-Based Evidence for a Pro-Oncogenic Role of ESRP1 in Human Colorectal Cancer Cells. International journal of molecular sciences 14 31963158
2023 Downregulated ESRP1/2 promotes lung metastasis of bladder carcinoma through altering FGFR2 splicing and macrophage polarization. Frontiers in immunology 13 37090731
2018 Silencing the Snail-Dependent RNA Splice Regulator ESRP1 Drives Malignant Transformation of Human Pulmonary Epithelial Cells. Cancer research 13 29431637
2022 The global Protein-RNA interaction map of ESRP1 defines a post-transcriptional program that is essential for epithelial cell function. iScience 12 36238894
2021 The RNA-Binding Protein ESRP1 Modulates the Expression of RAC1b in Colorectal Cancer Cells. Cancers 12 34439247
2021 MiR-337-3p suppresses migration and invasion of breast cancer cells by downregulating ESRP1. Acta histochemica 11 34481218
2016 Epithelial Splicing Regulatory Protein 1 (ESRP1) is a new regulator of stomach smooth muscle development and plasticity. Developmental biology 10 27108394
2022 Silencing ESRP1 expression promotes caspase-independent cell death via nuclear translocation of AIF in colon cancer cells. Cellular signalling 9 34986387
2018 ESRP1-Induced CD44 v3 Is Important for Controlling Pluripotency in Human Pluripotent Stem Cells. Stem cells (Dayton, Ohio) 9 29873154
2024 Functional analysis of ESRP1/2 gene variants and CTNND1 isoforms in orofacial cleft pathogenesis. Communications biology 8 39179789
2023 The Role of ESRP1 in the Regulation of PHGDH in Estrogen Receptor-Positive Breast Cancer. Laboratory investigation; a journal of technical methods and pathology 8 36925195
2025 The role of ESRP1 in solid tumor development through the regulation of CD44 splicing and EMT processes. Frontiers in oncology 5 40046628
2018 Esrp1 is a marker of mouse fetal germ cells and differentially expressed during spermatogenesis. PloS one 5 29324788
2024 Potential impact of epithelial splicing regulatory protein 1 (ESRP1) associated with tumor immunity in pancreatic adenocarcinoma. Journal of proteomics 3 39127164
2019 Expression of ESRP1 at human fetomaternal interface and involvement in trophoblast migration and invasion. Placenta 2 32056547
2026 A ESRP1/circPHGDH/miR-149/RAP1B positive feedback loop promotes the malignant behaviors and glycolysis of prostate cancer cell. Experimental & molecular medicine 1 41760734
2025 Esrp1 and Esrp2 Regulate the Stability of tmc1/2a mRNAs in Zebrafish Sensory Hair Cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 1 40086870
2025 Isoform switching in the CD44/ESRP1 axis as a driver of EMT and cancer stemness across tumor types. Biochimie 1 41130441
2024 Splicing factor ESRP1 derived circ_0068162 promotes the progression of oral squamous cell carcinoma via the miR-186/JAG axis. Carcinogenesis 1 37966490
2026 ESRP1 drives epithelial-mesenchymal transition by activating EPAC-RAP1A signaling axis. Frontiers in medicine 0 41728622
2026 ESRP1-Associated CD44 Alternative Splicing Stratifies Epithelial-Mesenchymal Identity States in a Non-Transformed Human Cell System. Current issues in molecular biology 0 41751394
2025 Genetic requirement for Esrp1/2 in vertebrate pituitary morphogenesis. medRxiv : the preprint server for health sciences 0 40236426
2025 ESRP1 exerts anti-tumor role by promoting ferroptosis in diffuse-type gastric cancer. Journal of experimental & clinical cancer research : CR 0 40528239
2025 ESRP1 drives subtype-specific breast cancer progression through ER-regulated transcriptional programs and EMT-related splicing switch. American journal of cancer research 0 40667548
2025 The ESRP1 promoter reporter can function as an in vivo sensor of DNA methyltransferase inhibition. BMC biotechnology 0 40866976
2025 Genetic requirement for Esrp1 and Esrp2 in vertebrate pituitary morphogenesis. Development (Cambridge, England) 0 41111330
2025 EMT-induced stem cell and mesenchymal programs can be decoupled via cell division and ESRP1-dependent mechanisms. iScience 0 41503216
2024 Functional analysis of ESRP1/2 gene variants and CTNND1 isoforms in orofacial cleft pathogenesis. bioRxiv : the preprint server for biology 0 39005284
2015 [The myeloid cell leukemia-1 mRNA splicing mediated by epithelial splicing regulatory protein 1 (ESRP1) in glioma U251 cell lines]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 26522352

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