Affinage

EPCAM

Epithelial cell adhesion molecule · UniProt P16422

Length
314 aa
Mass
34.9 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EpCAM is a transmembrane glycoprotein that functions as a signaling hub in epithelial proliferation, adhesion, and differentiation through regulated intramembrane proteolysis (RIP) and direct modulation of multiple signaling pathways. TACE-mediated ectodomain shedding followed by presenilin-2 cleavage releases a soluble ectodomain (EpEX) that activates EGFR and HGFR to stimulate ERK, AKT, and FAK signaling, and an intracellular domain (EpICD) that forms a nuclear complex with FHL2, β-catenin, and Lef-1 to drive transcription of c-myc and cyclin D1, promoting cell-cycle progression (PMID:19136966, PMID:15195135, PMID:22391566, PMID:29981429, PMID:37543570). EpCAM directly inhibits novel PKC isoforms via a pseudosubstrate motif in its cytoplasmic tail, thereby restraining actomyosin contractility and maintaining cadherin-mediated adhesion, and it physically associates with claudin-7 through a transmembrane AxxxG motif to protect claudins from matriptase-initiated lysosomal degradation — a mechanism whose disruption causes congenital tufting enteropathy (PMID:24183651, PMID:23486470, PMID:19276185, PMID:28094766, PMID:18572020). Germline 3′ deletions of EPCAM additionally cause epigenetic silencing of the adjacent MSH2 gene, resulting in Lynch syndrome (PMID:21309036).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2004 High

    Establishing that EpCAM is not merely an adhesion molecule but an active signaling receptor whose intracellular domain is necessary and sufficient for upregulating c-myc and cyclins and promoting proliferation answered the fundamental question of whether EpCAM has cell-autonomous oncogenic signaling capacity.

    Evidence Domain-swap mutagenesis with gain/loss-of-function in HEK293 and NIH3T3 cells; siRNA knockdown in breast cancer lines with proliferation, migration, and cadherin fractionation readouts

    PMID:15195135 PMID:15313925

    Open questions at the time
    • Protease responsible for EpICD release unknown
    • Identity of nuclear partners of EpICD not yet defined
    • Mechanism linking EpCAM to E-cadherin regulation unclear
  2. 2008 High

    Identification of homozygous EPCAM mutations as the genetic cause of congenital tufting enteropathy established EpCAM as essential for intestinal epithelial integrity and linked it to a Mendelian disease.

    Evidence SNP homozygosity mapping and sequencing in multiple unrelated CTE families; immunohistochemistry confirming protein loss in patient intestinal tissue

    PMID:18572020

    Open questions at the time
    • Molecular mechanism of epithelial disruption upon EpCAM loss not defined
    • Claudin interactions not yet identified
  3. 2009 High

    Discovery of the complete regulated intramembrane proteolysis (RIP) cascade — TACE ectodomain shedding followed by presenilin-2 cleavage releasing EpICD, which assembles a nuclear FHL2/β-catenin/Lef-1 transcription complex — provided the full mechanistic pathway from membrane to gene activation.

    Evidence Pharmacological and siRNA inhibition of TACE and presenilin-2; nuclear fractionation and co-IP of EpICD complex; reporter assays; xenograft tumorigenesis; cell-contact density experiments showing juxtacrine initiation

    PMID:19136966 PMID:19925656

    Open questions at the time
    • Crystal structure of EpICD-containing nuclear complex unavailable
    • Upstream signals triggering TACE activation at cell contacts not defined
  4. 2009 High

    Mapping the EpCAM–claudin-7 interaction to a transmembrane AxxxG motif and demonstrating that this complex is recruited to tetraspanin-enriched microdomains (TEMs) where it sustains ERK1/2 signaling and drug resistance revealed a second, adhesion-independent oncogenic function of EpCAM.

    Evidence Deletion and point-mutant constructs in HEK293/BSp73AS cells; co-IP; TEM fractionation; proliferation, migration, and tumorigenicity assays

    PMID:19276185

    Open questions at the time
    • Structural basis of the AxxxG-mediated transmembrane interaction not resolved
    • Relative contributions of RIP signaling versus TEM-based signaling to tumorigenesis unclear
  5. 2011 High

    Demonstration that 3′ EPCAM deletions cause read-through transcription and epigenetic silencing of MSH2 defined a cis-regulatory mechanism for Lynch syndrome independent of MSH2 coding mutations.

    Evidence MLPA and MSH2 promoter methylation analysis in 45 carrier families; tissue-specific expression profiling

    PMID:21309036

    Open questions at the time
    • Precise chromatin mechanism of read-through-induced silencing not fully dissected
    • Genotype–phenotype correlation for different deletion sizes incomplete
  6. 2012 High

    Identification of cyclin D1 as a direct transcriptional target of EpICD–FHL2 signaling, with consequent Rb phosphorylation, connected EpCAM proteolytic signaling to a canonical cell-cycle progression mechanism.

    Evidence EpCAM overexpression/knockdown; cyclin D1 promoter reporter; co-IP of EpICD–FHL2; Ki67 and cyclin D1 IHC in patient tumors

    PMID:22391566

    Open questions at the time
    • Full set of EpICD transcriptional targets undefined
    • Chromatin occupancy by the EpICD complex not mapped genome-wide
  7. 2013 High

    Discovery that EpCAM's cytoplasmic tail contains a pseudosubstrate motif that directly inhibits novel PKC isoforms, thereby restraining myosin contractility and preserving cadherin adhesion, established a proteolysis-independent signaling function for full-length EpCAM.

    Evidence In vitro PKC binding assay with synthetic cytoplasmic-tail peptides; mutagenesis; Xenopus embryo loss-of-function with actomyosin and cadherin phenotyping

    PMID:24183651

    Open questions at the time
    • Whether nPKC inhibition is operative in mammalian epithelia not confirmed
    • Relative importance of PKC-inhibitory versus RIP functions in CTE pathogenesis unknown
  8. 2013 High

    Showing that EpCAM protects claudin-7 and claudin-1 from lysosomal degradation, and that CTE-causing EpCAM mutations ablate EpCAM–claudin-7 complex formation causing intestinal barrier dysfunction, provided a molecular explanation for congenital tufting enteropathy.

    Evidence Reciprocal co-IP; shRNA knockdown with lysosome inhibitor rescue; conditional EpCAM-knockout mouse; electron microscopy; barrier permeability and ion transport assays; comparison with CTE patient tissue

    PMID:23486470 PMID:24337010

    Open questions at the time
    • Whether claudin destabilization alone accounts for the full CTE phenotype is untested
    • Role of desmosome alterations observed in KO mice not mechanistically dissected
  9. 2017 High

    Identification of matriptase as the protease cleaving EpCAM at Arg80, with HAI-2 as its inhibitor, showed that uncontrolled matriptase activity phenocopies CTE by destabilizing the EpCAM–claudin-7 complex via ectodomain cleavage.

    Evidence In vitro cleavage with purified proteins; HAI-2 knockout mouse; co-IP; CTE mutant rescue

    PMID:28094766

    Open questions at the time
    • Whether matriptase cleavage feeds into RIP-dependent EpICD signaling or only triggers degradation is unclear
    • Tissue-specific regulation of matriptase/HAI balance not mapped comprehensively
  10. 2018 High

    Biophysical evidence that EpCAM does not mediate intercellular homophilic adhesion but forms cis-dimers at pre-existing contacts overturned the long-held model of EpCAM as a cell-adhesion molecule and reframed it primarily as a signaling receptor.

    Evidence SAXS, cross-linking mass spectrometry, bead aggregation assay, and FLIM-FRET on live cells

    PMID:30185875

    Open questions at the time
    • Functional role of cis-dimerization not established
    • Whether cis-dimers are the signaling-competent unit for RIP is untested
  11. 2018 Medium

    Showing that the shed ectodomain EpEX activates EGFR–ERK1/2 signaling to promote proliferation and migration, and that this pathway feeds back to stimulate further EpCAM RIP and nuclear β-catenin accumulation, established a positive-feedback loop linking extracellular and intracellular EpCAM signals.

    Evidence EGFR/MEK inhibitor treatment; EpEX stimulation; co-IP; xenograft models; colorectal cancer tissue analysis

    PMID:29981429

    Open questions at the time
    • Direct EpEX–EGFR binding site not mapped
    • Relative importance of autocrine versus paracrine EpEX signaling in vivo unknown
  12. 2020 Medium

    Super-resolution imaging revealed that EpCAM forms heterogeneous nanoclusters within CD9-positive tetraspanin microdomains, regulated by cytoskeletal integrity and N-glycosylation, providing a spatial framework for its signaling functions. Parallel work confirmed functional redundancy between EpCAM and TROP2 in stabilizing claudins against matriptase-mediated degradation.

    Evidence dSTORM with CD9 knockdown and pharmacological perturbations; in vitro cleavage assays with siRNA knockdown of EpCAM/TROP2/matriptase/HAI-1/HAI-2 in keratinocytes

    PMID:31876148 PMID:32326212

    Open questions at the time
    • How nanocluster organization relates to RIP activation is unknown
    • TROP2 redundancy complicates tissue-specific phenotype predictions
  13. 2023 Medium

    Demonstration that EpEX directly binds HGFR (c-Met) and cooperates with HGF to activate ERK and FAK-AKT signaling, stabilize β-catenin/Snail, and promote EMT and metastasis expanded the receptor repertoire of shed EpEX beyond EGFR.

    Evidence Co-IP, FRET, ELISA for direct EpEX–HGFR interaction; migration/invasion assays; orthotopic and tail-vein metastasis mouse models

    PMID:37543570

    Open questions at the time
    • EpEX binding site on HGFR not mapped structurally
    • Whether EpEX activates additional RTKs is unknown
    • Relative contribution of EGFR versus HGFR arm in vivo not delineated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how cis-dimerization and nanocluster organization couple to RIP initiation, the genome-wide transcriptional program of the EpICD nuclear complex, and how the PKC-inhibitory and claudin-stabilizing functions of full-length EpCAM are coordinated with proteolytic signaling in different epithelial contexts.
  • No ChIP-seq or CUT&RUN mapping of EpICD-containing complex
  • Structural basis of EpICD–FHL2–β-catenin–Lef-1 assembly unknown
  • Relative contribution of PKC inhibition versus RIP signaling to epithelial homeostasis not dissected in mammalian models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0048018 receptor ligand activity 2 GO:0098631 cell adhesion mediator activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1500931 Cell-Cell communication 2 R-HSA-1640170 Cell Cycle 2 R-HSA-1643685 Disease 2
Partners
CD9CLDN1CLDN7CTNNB1EGFRFHL2ITGB1MET
Complex memberships
EpCAM–claudin-7 membrane complexEpICD/FHL2/β-catenin/Lef-1 nuclear transcription complexTetraspanin-enriched microdomain (TEM) complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 EpCAM undergoes regulated intramembrane proteolysis (RIP): TACE sequentially sheds the ectodomain (EpEX) and presenilin-2 cleaves the remaining stub, releasing the intracellular domain (EpICD). EpICD then associates with FHL2, β-catenin, and Lef-1 to form a nuclear complex that contacts DNA at Lef-1 consensus sites, induces target gene transcription (including c-myc), and is oncogenic in immunodeficient mice. Pharmacological inhibition and genetic silencing of TACE and presenilin-2; nuclear fractionation; Co-IP of EpICD/FHL2/β-catenin/Lef-1 complex; reporter assays; xenograft tumor formation Nature cell biology High 19136966
2004 The intracellular domain of EpCAM is necessary and sufficient to upregulate c-myc and cyclins A/E, reduce growth-factor dependence, and enhance colony formation, establishing a direct link between EpCAM intracellular signaling and cell-cycle progression. Domain-swapping experiments; antisense-mediated knockdown; metabolic activity and colony formation assays in human 293 cells and NIH3T3 fibroblasts Oncogene High 15195135
2004 Silencing EpCAM with siRNA decreases breast cancer cell proliferation, migration, and invasion, and increases the detergent-insoluble (membrane-associated) fractions of E-cadherin, α-catenin, and β-catenin, indicating EpCAM negatively regulates E-cadherin-mediated adhesion complexes. siRNA knockdown; proliferation, migration, and invasion assays; detergent-solubility fractionation of cadherin/catenin complexes Cancer research Medium 15313925
2009 Initial activation of EpCAM cleavage requires cell-to-cell contact (juxtacrine signaling); once EpEX is released it can act in a paracrine manner. EpICD-driven nuclear translocation and c-myc induction require the cleavage step and subsequent nuclear import. Confocal microscopy; immunoblotting; conditional cell-density experiments; conditional EpICD expression system BMC cancer Medium 19925656
2012 EpCAM promotes cell-cycle progression by transcriptionally upregulating cyclin D1 in a manner dependent on its direct interaction partner FHL2; downstream consequences include Rb phosphorylation and induction of cyclins E and A. EpCAM overexpression and knockdown; cyclin D1 promoter assays; co-IP of EpICD–FHL2; immunohistochemistry for Ki67, cyclin D1, and phospho-Rb in patient tumors Oncogene High 22391566
2013 EpCAM physically associates with claudin-7 (and claudin-1 via claudin-7) and protects them from lysosomal degradation; EpCAM knockdown reduces claudin-7 and claudin-1 protein levels and paradoxically increases their accumulation at tight junctions, altering trans-epithelial resistance. Preparative immunoprecipitation; co-IP; shRNA knockdown; trans-epithelial electroresistance measurements; immunofluorescence microscopy with lysosome inhibitors The Journal of biological chemistry High 23486470
2009 EpCAM–claudin-7 interaction requires an AxxxG motif in EpCAM's transmembrane region; the resulting complex is recruited into tetraspanin-enriched membrane microdomains (TEMs) where it supports sustained ERK1/2 phosphorylation, upregulation of anti-apoptotic proteins, drug resistance, and enhanced cell motility, but abolishes EpCAM-mediated homophilic adhesion. Transfection of deletion and point-mutant EpCAM/claudin-7 constructs in HEK293 and BSp73AS cells; co-IP; TEM fractionation; proliferation, migration, and tumorigenicity assays Molecular cancer research High 19276185
2013 EpCAM acts as a potent inhibitor of novel PKC (nPKC) via a short pseudosubstrate-like segment in its cytoplasmic tail that binds nPKCs with high affinity; loss of EpCAM in Xenopus embryos leads to PKC overstimulation, ERK pathway hyperactivation, exacerbated myosin contractility, loss of cadherin-mediated adhesion, and tissue dissociation. Xenopus embryo loss-of-function; in vitro PKC binding assay with cytoplasmic tail peptides; mutagenesis; myosin contractility measurements; cadherin adhesion assays Developmental cell High 24183651
2017 Matriptase cleaves EpCAM after Arg80; loss of the matriptase inhibitor HAI-2 in intestinal epithelial cells leads to unrestrained matriptase activity, efficient EpCAM cleavage, reduced EpCAM–claudin-7 association, and lysosomal degradation of both EpCAM and claudin-7, causing intestinal epithelial dysplasia (congenital tufting enteropathy phenotype). In vitro cleavage of purified recombinant proteins; cell transfection; HAI-2 knockout mouse model; immunoprecipitation; HAI-2 CTE mutant functional rescue experiments The Journal of clinical investigation High 28094766
2018 EpCAM homo-oligomerization does not mediate intercellular adhesion; EpCAM monomers do not form inter-cellular oligomers detectable by SAXS or XL-MS, and bead aggregation assays confirm no homophilic adhesion. EpCAM forms stable cis-dimers on the cell surface at pre-formed cell–cell contacts as detected by FLIM-FRET. SAXS; cross-linking mass spectrometry (XL-MS); bead aggregation assay; FLIM-FRET on live cells Scientific reports High 30185875
2018 The extracellular domain of EpCAM (EpEX) activates EGFR and downstream ERK1/2 signaling to promote colon cancer cell migration and proliferation; EpEX–EGFR–ERK1/2 signaling positively regulates RIP of EpCAM and EpICD shedding, which then drives nuclear β-catenin accumulation and HIF1α target gene expression. EGFR/MEK inhibitor treatment; EpEX-stimulation assays; immunoprecipitation; Western blotting; xenograft tumor models; analysis of colorectal cancer tissues Cancer letters Medium 29981429
2011 EpCAM and its complex partner claudin-7 (Cldn7) facilitate transcription-factor-mediated somatic cell reprogramming to iPSCs; overexpression of EpCAM or EpICD enhances reprogramming efficiency, activates the Oct4 promoter, and suppresses p53 and p21 expression. Quantitative RT-PCR; alkaline phosphatase and Nanog colony assays; EpCAM/EpICD overexpression; shRNA knockdown; Oct4 promoter reporter assay; iPSC characterization in vitro and in vivo The Journal of biological chemistry Medium 21799003
2008 Mutations in EPCAM (including a splice-site mutation causing deletion of exon 4) are the genetic cause of congenital tufting enteropathy, resulting in loss of EpCAM protein from intestinal epithelium. SNP homozygosity mapping; direct DNA sequencing; RT-PCR; immunohistochemistry; Western blotting of patient intestinal tissue Gastroenterology High 18572020
2011 3′-end deletions of EPCAM encompassing the transcription termination signal cause allele-specific epigenetic silencing (promoter hypermethylation) of the neighboring DNA mismatch repair gene MSH2 in tissues expressing EPCAM, leading to Lynch syndrome. Multiplex ligation-dependent probe amplification (MLPA); MSH2 promoter methylation analysis; tissue-specific expression profiling in germline deletion carriers Human mutation High 21309036
2013 EpCAM mutation (exon 4 deletion) causes loss of EpCAM–claudin-7 colocalization and complex formation in vivo, leading to intestinal barrier dysfunction (increased permeability, reduced ion transport, altered desmosomes) and the CTE pathological phenotype. Cre-LoxP conditional mouse model; histology; electron microscopy; immunohistochemistry; barrier permeability assays; ion transport measurements; comparison with CTE patient tissue American journal of physiology. Gastrointestinal and liver physiology High 24337010
2011 EpCAM signaling activates NF-κB, promotes c-Jun phosphorylation via the JNK pathway, and increases AP-1 transcription factor activity; soluble extracellular EpCAM (rEpEX) can rescue invasion, AP-1 activity, and c-Jun phosphorylation after EpCAM ablation. RNAi loss-of-function; gain-of-function with cDNA construct; recombinant EpEX rescue; phosphoprotein analysis; AP-1 and JNK reporter/inhibitor experiments; invasion assays in vitro and in vivo Breast cancer research Medium 22132731
2013 EpCAM ablation decreases NF-κB transcription factor activity and RELA phosphorylation, increases IκBα protein, and reduces IL-8 expression; forced expression of IκBα or RELA ablation blocks EpCAM-dependent rescue of IL-8 promoter activity. RNAi; constitutively active/dominant negative NF-κB constructs; IL-8 promoter reporter assay; ELISA; Western blotting Molecular cancer research Medium 23378578
2019 EpCAM associates with integrin β1 (shown by co-immunoprecipitation); EpCAM knockout reduces integrin α5 expression and decreases phosphorylation of FAK, AKT, and ERK, impairing cell adhesion, migration, and proliferation on extracellular matrix proteins. CRISPR/Cas9 EpCAM knockout; co-immunoprecipitation; Western blotting for FAK/AKT/ERK phosphorylation; adhesion and migration assays Biochemical and biophysical research communications Medium 31806375
2020 EpCAM organizes into heterogeneous clusters on the cell membrane and localizes within tetraspanin-enriched microdomains (TEMs) through co-association with CD9; cytoskeleton integrity and N-glycosylation both limit EpCAM cluster assembly. Direct stochastic optical reconstruction microscopy (dSTORM) with fluorophore-conjugated peptides; dual-color super-resolution imaging; CD9 knockdown; cytoskeleton disruption; glycosylation inhibition Analytical chemistry Medium 31876148
2020 Matriptase cleaves both EpCAM and its homolog TROP2 in keratinocytes; EpCAM and TROP2 are redundant in stabilizing claudin-1 and claudin-7 (knockdown of either alone has small effects, but combined knockdown markedly reduces claudins); HAI-1 (not HAI-2) is the principal physiological inhibitor of matriptase in keratinocytes. In vitro cleavage of purified recombinant proteins; siRNA knockdown of EpCAM, TROP2, HAI-1, HAI-2, matriptase in HaCaT cells; Western blotting; lysosome inhibitor (chloroquine) rescue Cells High 32326212
2023 The extracellular domain of EpCAM (EpEX) binds directly to HGFR (c-Met) and cooperates with HGF to activate downstream ERK and FAK-AKT signaling; EpEX stabilizes β-catenin and Snail by decreasing GSK3β activity, promoting EMT and metastasis in colon cancer. Immunoprecipitation; ELISA; FRET; Western blotting; migration/invasion assays; tail vein injection and orthotopic metastasis mouse models Journal of translational medicine Medium 37543570

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Nuclear signalling by tumour-associated antigen EpCAM. Nature cell biology 564 19136966
2004 EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer research 442 15313925
2009 The emerging role of EpCAM in cancer and stem cell signaling. Cancer research 433 19584271
2004 The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene 296 15195135
2020 Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years? Cancer metastasis reviews 258 32507912
2010 EpCAM in carcinogenesis: the good, the bad or the ugly. Carcinogenesis 255 20837599
2011 EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis. Journal of clinical pathology 231 21415054
2013 EpCAM: structure and function in health and disease. Biochimica et biophysica acta 227 23618806
2015 The detection of EpCAM(+) and EpCAM(-) circulating tumor cells. Scientific reports 223 26184843
1990 Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2. Proceedings of the National Academy of Sciences of the United States of America 165 2333300
2008 Identification of EpCAM as the gene for congenital tufting enteropathy. Gastroenterology 157 18572020
2008 CD44 and EpCAM: cancer-initiating cell markers. Current molecular medicine 148 19075676
2019 Biology and clinical relevance of EpCAM. Cell stress 140 31225512
2018 Functions of EpCAM in physiological processes and diseases (Review). International journal of molecular medicine 128 30015855
2011 Recurrence and variability of germline EPCAM deletions in Lynch syndrome. Human mutation 123 21309036
2013 Epithelial cell adhesion molecule (EpCAM) regulates claudin dynamics and tight junctions. The Journal of biological chemistry 112 23486470
2012 EpCAM regulates cell cycle progression via control of cyclin D1 expression. Oncogene 99 22391566
2009 Claudin-7 regulates EpCAM-mediated functions in tumor progression. Molecular cancer research : MCR 99 19276185
2011 Circulating tumor cells and EpCAM expression in neuroendocrine tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 90 21224371
2018 Antibody Based EpCAM Targeted Therapy of Cancer, Review and Update. Current cancer drug targets 87 29295696
2020 Revisiting the Roles of Pro-Metastatic EpCAM in Cancer. Biomolecules 83 32046162
2007 EpCAM an immunotherapeutic target for gastrointestinal malignancy: current experience and future challenges. British journal of cancer 80 17325709
2005 Expression of epithelial cell adhesion molecule (EpCam) in renal epithelial tumors. The American journal of surgical pathology 79 15613858
2011 Epithelial cell adhesion molecule (EpCAM) complex proteins promote transcription factor-mediated pluripotency reprogramming. The Journal of biological chemistry 78 21799003
2021 Functional Implications of the Dynamic Regulation of EpCAM during Epithelial-to-Mesenchymal Transition. Biomolecules 74 34209658
2013 Context-dependent adaption of EpCAM expression in early systemic esophageal cancer. Oncogene 73 24141784
2022 Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside. Experimental hematology & oncology 72 36369033
2009 Epithelial cell adhesion molecule (EpCAM) is overexpressed in breast cancer metastases. Breast cancer research and treatment 72 20012351
2017 Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery. Theranostics 71 29158811
2018 Extracellular domain of EpCAM enhances tumor progression through EGFR signaling in colon cancer cells. Cancer letters 69 29981429
2015 Gene Knockdown by EpCAM Aptamer-siRNA Chimeras Suppresses Epithelial Breast Cancers and Their Tumor-Initiating Cells. Molecular cancer therapeutics 68 26264278
2015 EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using polymeric nanocomplex. Journal of biomedical science 66 25576037
2012 Role of the EpCAM (CD326) in prostate cancer metastasis and progression. Cancer metastasis reviews 65 22718399
2009 Initial activation of EpCAM cleavage via cell-to-cell contact. BMC cancer 65 19925656
2017 Matriptase-mediated cleavage of EpCAM destabilizes claudins and dysregulates intestinal epithelial homeostasis. The Journal of clinical investigation 63 28094766
2018 Lgr5+CD44+EpCAM+ Strictly Defines Cancer Stem Cells in Human Colorectal Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 59 29627827
2018 EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome. Human mutation 57 30461124
2021 Immunotherapy for breast cancer using EpCAM aptamer tumor-targeted gene knockdown. Proceedings of the National Academy of Sciences of the United States of America 55 33627408
1999 Autoantibodies against the tumour-associated antigen GA733-2 in patients with colorectal carcinoma. Cancer immunology, immunotherapy : CII 51 10203061
2019 Hypoxia modulates stem cell properties and induces EMT through N-glycosylation of EpCAM in breast cancer cells. Journal of cellular physiology 50 31584203
2020 A Novel Function for KLF4 in Modulating the De-differentiation of EpCAM-/CD133- nonStem Cells into EpCAM+/CD133+ Liver Cancer Stem Cells in HCC Cell Line HuH7. Cells 48 32408542
2013 EpCAM controls actomyosin contractility and cell adhesion by direct inhibition of PKC. Developmental cell 48 24183651
2013 Functional consequences of EpCam mutation in mice and men. American journal of physiology. Gastrointestinal and liver physiology 44 24337010
2012 The molecular basis of EPCAM expression loss in Lynch syndrome-associated tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 43 22388758
2015 An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer. Oncotarget 41 26317650
2010 Adecatumumab: an anti-EpCAM monoclonal antibody, from the bench to the bedside. Expert opinion on biological therapy 41 20426706
2014 Mutation of EpCAM leads to intestinal barrier and ion transport dysfunction. Journal of molecular medicine (Berlin, Germany) 40 25482158
2011 Activator protein 1 (AP-1) contributes to EpCAM-dependent breast cancer invasion. Breast cancer research : BCR 40 22132731
2019 Shedding light on the EpCAM: An overview. Journal of cellular physiology 39 30628064
2011 Dynamic changes in EPCAM expression during spermatogonial stem cell differentiation in the mouse testis. PloS one 39 21858196
2020 EpCAM cellular functions in adhesion and migration, and potential impact on invasion: A critical review. Biochimica et biophysica acta. Reviews on cancer 37 32976980
2014 Lynch-like syndrome: characterization and comparison with EPCAM deletion carriers. International journal of cancer 37 25110875
2015 The role of EpCAM in physiology and pathology of the epithelium. Histology and histopathology 35 26493939
2014 Coexpression of EpCAM, CD44 variant isoforms and claudin-7 in anaplastic thyroid carcinoma. PloS one 35 24727741
2013 Promoter hypomethylation of EpCAM-regulated bone morphogenetic protein gene family in recurrent endometrial cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 35 24077349
2015 EpCAM Aptamer-siRNA Chimera Targets and Regress Epithelial Cancer. PloS one 34 26176230
2016 The plastic cellular states of liver cells: Are EpCAM and Lgr5 fit for purpose? Hepatology (Baltimore, Md.) 33 26799921
2018 EpCAM homo-oligomerization is not the basis for its role in cell-cell adhesion. Scientific reports 32 30185875
2018 Epithelial cell adhesion molecule (EpCAM) is involved in prostate cancer chemotherapy/radiotherapy response in vivo. BMC cancer 32 30419852
2017 Selection and targeting of EpCAM protein by ssDNA aptamer. PloS one 32 29245156
2014 Expression of EpCAM increases in the hepatitis B related and the treatment-resistant hepatocellular carcinoma. BioMed research international 32 24696843
2013 Clinicopathologic implications of EpCAM and Sox2 expression in breast cancer. Clinical breast cancer 32 24201161
2013 EpCAM modulates NF-κB signaling and interleukin-8 expression in breast cancer. Molecular cancer research : MCR 31 23378578
2020 Quantitatively Mapping the Assembly Pattern of EpCAM on Cell Membranes with Peptide Probes. Analytical chemistry 30 31876148
2017 EpCAM-based assays for epithelial tumor cell detection in cerebrospinal fluid. Journal of neuro-oncology 30 29192390
2024 Regulation of the Function and Expression of EpCAM. Biomedicines 29 38791091
2020 Matriptase Cleaves EpCAM and TROP2 in Keratinocytes, Destabilizing Both Proteins and Associated Claudins. Cells 29 32326212
2013 High EpCAM expression is linked to proliferation and lauren classification in gastric cancer. BMC research notes 29 23830302
2019 MM-131, a bispecific anti-Met/EpCAM mAb, inhibits HGF-dependent and HGF-independent Met signaling through concurrent binding to EpCAM. Proceedings of the National Academy of Sciences of the United States of America 28 30898885
2018 EpCAM duality becomes this molecule in a new Dr. Jekyll and Mr. Hyde tale. Critical reviews in oncology/hematology 28 29759567
2015 Expression of EpCAM and Wnt/ β-catenin in human colon cancer. Genetics and molecular research : GMR 28 25966221
2017 Cooverexpression of EpCAM and c-myc genes in malignant breast tumours. Journal of genetics 27 28360395
2019 CD44, TGM2 and EpCAM as novel plasma markers in endometrial cancer diagnosis. BMC cancer 26 31035965
2015 Circulating tumor cells isolation: the "post-EpCAM era". Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 25 26543332
2021 EpCAM-Mediated Cellular Plasticity Promotes Radiation Resistance and Metastasis in Breast Cancer. Frontiers in cell and developmental biology 24 33490064
2019 EpCAM associates with integrin and regulates cell adhesion in cancer cells. Biochemical and biophysical research communications 24 31806375
2017 Mutation of N-linked glycosylation in EpCAM affected cell adhesion in breast cancer cells. Biological chemistry 24 28315854
2017 Enrichment, Isolation and Molecular Characterization of EpCAM-Negative Circulating Tumor Cells. Advances in experimental medicine and biology 24 28560675
2019 Immunocyte Profiling Using Single-Cell Mass Cytometry Reveals EpCAM+ CD4+ T Cells Abnormal in Colon Cancer. Frontiers in immunology 23 31354723
2016 Expression of CEA, CA19-9, CA125, and EpCAM in pseudomyxoma peritonei. Human pathology 23 27038681
2012 EpCAM is a putative stem marker in retinoblastoma and an effective target for T-cell-mediated immunotherapy. Molecular vision 23 22328825
2020 Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1. International journal of molecular sciences 22 32392820
2014 Overexpression of EpCAM and Trop2 in pituitary adenomas. International journal of clinical and experimental pathology 22 25550831
2020 Current View on EpCAM Structural Biology. Cells 21 32486423
2019 Genome-Wide RNAi Screen Identifies PMPCB as a Therapeutic Vulnerability in EpCAM+ Hepatocellular Carcinoma. Cancer research 21 30862714
2017 Upregulation of LncRNA BCYRN1 promotes tumor progression and enhances EpCAM expression in gastric carcinoma. Oncotarget 21 29435146
2008 EpCAM in morphogenesis. Frontiers in bioscience : a journal and virtual library 21 18508569
2014 EpCAM, a potential therapeutic target for esophageal squamous cell carcinoma. Annals of surgical oncology 20 24566863
2014 The overexpression of epithelial cell adhesion molecule (EpCAM) in glioma. Journal of neuro-oncology 20 24906438
2022 Development of a Novel Anti-EpCAM Monoclonal Antibody for Various Applications. Antibodies (Basel, Switzerland) 19 35735360
2020 EpCAM as Modulator of Tissue Plasticity. Cells 19 32961790
2011 EpCAM- and EGFR-targeted selective gene therapy for biliary cancers using Z33-fiber-modified adenovirus. International journal of cancer 19 21710497
2023 Epithelial cell adhesion molecule (EpCAM) regulates HGFR signaling to promote colon cancer progression and metastasis. Journal of translational medicine 18 37543570
2003 Expression of MUC 1 and Ep-CAM in Merkel cell carcinomas: implications for immunotherapy. Archives of dermatological research 18 12844224
1999 Evaluating GA733-2 mRNA as a marker for the detection of micrometastatic breast cancer in peripheral blood and bone marrow. Archives of gynecology and obstetrics 18 10728619
2018 Drug-induced expression of EpCAM contributes to therapy resistance in esophageal adenocarcinoma. Cellular oncology (Dordrecht, Netherlands) 17 30116994
2020 The Biodistribution of a CD3 and EpCAM Bispecific T-Cell Engager Is Driven by the CD3 Arm. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 16 32284393
2022 Combined Targeting of AKT and mTOR Inhibits Tumor Formation of EpCAM+ and CD90+ Human Hepatocellular Carcinoma Cells in an Orthotopic Mouse Model. Cancers 14 35454789
2014 EpCAM knockdown alters microRNA expression in retinoblastoma--functional implication of EpCAM regulated miRNA in tumor progression. PloS one 14 25502397
2017 EPCAM Expression in Colon Adenocarcinoma and its Relationship with TNM Staging. Advanced biomedical research 13 28553629