Affinage

EPCAM

Epithelial cell adhesion molecule · UniProt P16422

Length
314 aa
Mass
34.9 kDa
Annotated
2026-06-09
100 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EpCAM is a transmembrane epithelial glycoprotein that integrates cell-contact-dependent proliferative signaling with epithelial barrier maintenance (PMID:19136966, PMID:23486470). Its extracellular domain adopts a characteristic disulfide architecture with a thyroglobulin type-1A region, and the full-length protein assembles into high-affinity non-covalent cis-dimers (PMID:11080501, PMID:11058587). Upon cell-cell contact, EpCAM undergoes regulated intramembrane proteolysis: TACE sheds the EpEX ectodomain and presenilin-2 releases the intracellular domain EpICD, which translocates to the nucleus and forms a transcriptional complex with FHL2, beta-catenin, and Lef-1 to drive proliferative target genes including c-myc and cyclin D1, the latter feeding Rb phosphorylation and cell-cycle progression (PMID:19136966, PMID:19925656, PMID:22391566). The shed EpEX ectodomain acts as a ligand for receptor tyrosine kinases: it binds EGFR to activate AKT/MAPK signaling that stabilizes PD-L1 and suppresses FOXO3a, and binds HGFR (c-Met) to cooperate with HGF in activating ERK and FAK-AKT signaling, stabilizing beta-catenin and Snail to promote EMT and metastasis (PMID:32978170, PMID:37543570). In parallel, EpCAM physically associates with claudin-7 (and indirectly claudin-1), protecting these tight-junction proteins from lysosomal degradation; this stabilizing role is shared redundantly with TROP2 and is abolished by matriptase cleavage of EpCAM and TROP2 (PMID:23486470, PMID:32326212, PMID:35730316). Through its cytoplasmic tail, a pseudosubstrate-like motif directly inhibits novel PKC, restraining Erk activity and myosin contractility to preserve cadherin-mediated adhesion and tissue integrity (PMID:24183651). Loss of EpCAM function via exon-4 deletion disrupts the EpCAM/claudin-7 complex and increases intestinal permeability, the basis of congenital tufting enteropathy (PMID:24337010, PMID:25482158). Structural and biophysical analyses establish that EpCAM forms cis-dimers but not intercellular trans-oligomers, arguing against a direct homophilic cell-cell adhesion function (PMID:30185875).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1994 Medium

    Established that the amplifiability of the EpCAM/TROP1 locus is controlled by DNA methylation, providing the first regulatory handle on its genomic behavior in cancer cells.

    Evidence 5-azacytidine demethylation, transfection, and Southern blot copy-number analysis in JAR choriocarcinoma cells

    PMID:8016075

    Open questions at the time
    • Does not address the protein's function
    • Mechanism of methylation control at the endogenous locus not defined
  2. 2000 High

    Defined EpCAM's extracellular disulfide architecture, glycosylation sites, and showed it exists as non-covalent cis-dimers whose oligomeric state is required for cell aggregation activity, framing it as a putative adhesion molecule.

    Evidence MALDI-MS, peptide sequencing, sedimentation equilibrium, cross-linking, and cell aggregation inhibition assays on purified GA733-2/EpCAM

    PMID:11058587 PMID:11080501

    Open questions at the time
    • Whether dimers act in cis or trans not resolved by these methods
    • No high-resolution structure of the intact protein
  3. 2003 Medium

    Connected loss of p53 to demethylation and amplification of the EpCAM/TROP1 gene, defining a p53→methylation→amplification axis relevant to tumorigenesis.

    Evidence wtTP53 reintroduction into p53-null cells with Southern blot methylation/copy-number analysis and in vitro Sss I methylation control

    PMID:12642870

    Open questions at the time
    • Direct mechanism linking p53 to locus methylation unknown
    • Single lab
  4. 2009 High

    Resolved how EpCAM signals by demonstrating sequential TACE/presenilin-2 proteolysis releasing nuclear EpICD that complexes with FHL2/beta-catenin/Lef-1 to drive oncogenic transcription, and that this requires cell-cell contact.

    Evidence Protease inhibition, siRNA silencing, nuclear fractionation, xenograft oncogenesis, and density-dependent culture with pre-cleaved EpICD constructs

    PMID:19136966 PMID:19925656

    Open questions at the time
    • Trigger coupling contact to TACE activity not molecularly defined
    • Identity of all EpICD target genes incomplete
  5. 2012 Medium

    Linked EpICD signaling to the cell cycle by showing FHL2-dependent cyclin D1 transcription, Rb phosphorylation, and induction of cyclins E and A.

    Evidence EpCAM knockdown/overexpression, cyclin RT-PCR/Western, FHL2 co-depletion rescue, and patient-tissue IHC

    PMID:22391566

    Open questions at the time
    • Direct promoter occupancy by EpICD/FHL2 not shown
    • Single lab
  6. 2013 High

    Identified EpCAM's barrier function: it binds claudin-7 (and indirectly claudin-1) to protect them from lysosomal degradation, and validated this in a CTE mouse model and patient tissue.

    Evidence Reciprocal co-IP, knockdown with lysosomal-inhibitor rescue, TEER assays, and Epcam exon-4-deletion mouse with patient tissue confirmation

    PMID:23486470 PMID:24337010

    Open questions at the time
    • Structural basis of EpCAM-claudin-7 interaction not defined
    • Paradoxical TJ accumulation on knockdown not fully explained
  7. 2013 High

    Revealed a contact-adhesion regulatory mechanism whereby EpCAM's cytoplasmic pseudosubstrate-like motif directly inhibits novel PKC to restrain Erk and myosin contractility and preserve tissue integrity.

    Evidence Xenopus loss-of-function, in vitro nPKC binding assays of the cytoplasmic tail, PKC/Erk/myosin readouts

    PMID:24183651

    Open questions at the time
    • Relationship between PKC inhibition and RIP signaling not integrated
    • Which nPKC isoforms in mammalian epithelia not specified
  8. 2013 Medium

    Positioned EpCAM upstream of an NF-kB/RELA/IL-8 invasion axis in breast cancer through epistatic rescue.

    Evidence EpCAM siRNA knockdown, NF-kB reporter, RELA/IkBa Westerns, IL-8 ELISA, and RELA/IkBa rescue experiments

    PMID:23378578

    Open questions at the time
    • Mechanism linking EpCAM to NF-kB activation unknown
    • Single lab and cell-type-specific
  9. 2014 High

    Quantified the barrier consequences of EpCAM loss, showing reduced electrical resistance, increased paracellular permeability, decreased ion transport, and reduced TJ protein expression.

    Evidence EpCAM shRNA in T84 cells and inducible Epcam exon-4-deletion mouse with TEER, permeability, ion transport, and Western readouts

    PMID:25482158

    Open questions at the time
    • Causal chain from claudin loss to ion transport defects not dissected
  10. 2015 Medium

    Demonstrated that a defined-epitope antibody blocking EpICD production reduces nuclear signaling and tumor growth, validating RIP-dependent signaling as a therapeutic target.

    Evidence Antibody epitope mapping, EpICD Westerns, apoptosis assays, and xenograft models

    PMID:26317650

    Open questions at the time
    • Mechanism by which epitope binding blocks cleavage unclear
    • Single lab
  11. 2018 High

    Challenged the homophilic-adhesion model by showing EpCAM forms cis-dimers but no detectable intercellular trans-oligomers.

    Evidence SAXS, cross-linking mass spectrometry, bead aggregation, and FLIM-FRET on cell surfaces

    PMID:30185875

    Open questions at the time
    • Functional role of the cis-dimer not fully defined
    • Cannot exclude weak transient trans-interactions below detection
  12. 2020 Medium

    Established that the shed EpEX ectodomain acts as an EGFR ligand activating AKT/MAPK to stabilize PD-L1 and suppress FOXO3a, linking EpCAM to immune evasion.

    Evidence Co-IP of EpEX with EGFR, signaling Westerns, FOXO3a immunofluorescence, neutralizing antibody, and in vivo metastasis/orthotopic models

    PMID:32978170

    Open questions at the time
    • Stoichiometry/affinity of EpEX-EGFR binding not quantified
    • Single lab
  13. 2020 High

    Showed matriptase cleaves EpCAM and TROP2 to destabilize claudins via lysosomal routing, with HAI proteins restraining this cleavage, defining a proteolytic switch on barrier integrity.

    Evidence In vitro cleavage with purified proteins, active-site mutant controls, HAI/matriptase knockdowns in HaCaT cells, and chloroquine rescue

    PMID:32326212

    Open questions at the time
    • Physiological contexts where matriptase regulates EpCAM in vivo not established
  14. 2019 Medium

    Identified an EpCAM-integrin beta1 association controlling FAK/ERK-dependent adhesion and migration.

    Evidence Co-IP, CRISPR/Cas9 knockout, phospho-FAK/AKT/ERK Westerns, adhesion/migration/colony assays in CW-2 and A431 cells

    PMID:31806375

    Open questions at the time
    • Direct vs indirect nature of EpCAM-integrin association unresolved
    • Single lab
  15. 2022 High

    Established genetic redundancy between EPCAM and TROP2 in claudin-7 stabilization and epithelial development using single and double knockout mice.

    Evidence Epcam, Trop2, and double-knockout mice with multi-tissue histology and claudin-7 immunofluorescence

    PMID:35730316

    Open questions at the time
    • Molecular basis of functional substitution not defined
    • Tissue-specific differences in redundancy not fully mapped
  16. 2023 Medium

    Extended EpEX ligand activity to HGFR (c-Met), showing cooperation with HGF to drive ERK/FAK-AKT signaling, beta-catenin/Snail stabilization, EMT, and metastasis.

    Evidence IP, ELISA, FRET for EpEX-HGFR interaction, signaling Westerns, invasion assays, and tail-vein/orthotopic metastasis models

    PMID:37543570

    Open questions at the time
    • Interplay between EpEX-EGFR and EpEX-HGFR signaling not reconciled
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EpCAM's distinct activities — RIP-driven nuclear transcription, EpEX-mediated RTK ligand function, claudin stabilization, integrin association, and PKC inhibition — are coordinated within a single cell and which dominate in specific tissue contexts remains unresolved.
  • No unified model integrating proteolytic, ligand, and scaffolding functions
  • Context-dependent dominance of each mechanism unknown
  • No full-length structure linking dimerization to function

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 2 GO:0140110 transcription regulator activity 2 GO:0140313 molecular sequestering activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1500931 Cell-Cell communication 2 R-HSA-1640170 Cell Cycle 1 R-HSA-1643685 Disease 1
Partners
CLDN1CLDN7CTNNB1EGFRFHL2ITGB1LEF1MET
Complex memberships
EpCAM-claudin-7 complexEpICD-FHL2-beta-catenin-Lef-1 transcriptional complex

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 EpCAM undergoes regulated intramembrane proteolysis (RIP): its ectodomain EpEX is shed by TACE, and the remaining stub is cleaved by presenilin-2 to release the intracellular domain EpICD, which translocates to the nucleus. Nuclear EpICD forms a complex with FHL2, β-catenin, and Lef-1 that binds Lef-1 consensus DNA sites, drives target gene transcription, and is oncogenic in immunodeficient mice. Pharmacological or genetic inhibition of either protease impairs EpCAM-dependent proliferative signaling. Pharmacological inhibition (TACE/presenilin-2 inhibitors), genetic silencing (siRNA), conditional cell systems, confocal microscopy, immunoblotting, nuclear fractionation, xenograft oncogenesis assay, patient tissue immunohistochemistry Nature cell biology High 19136966
2009 Activation of EpCAM's RIP-dependent oncogenic signaling requires cell-to-cell contact: when intercellular contact is prevented, EpCAM does not confer growth advantage. Contact triggers initial cleavage (juxtacrine), releasing soluble EpEX that can act in a paracrine manner. The pre-cleaved EpICD fragment bypasses the contact requirement but still requires nuclear translocation to induce c-myc and proliferation. Density-dependent cell culture experiments, conditional cell systems expressing pre-cleaved EpICD, confocal laser scanning microscopy, immunoblotting, cell counting, c-myc reporter assays BMC cancer Medium 19925656
2012 EpCAM drives cell cycle progression by upregulating cyclin D1 transcription in an FHL2-dependent manner. Downstream consequences include phosphorylation of retinoblastoma protein (Rb) and induction of cyclins E and A. In vivo, EpCAM expression level positively correlates with Ki67, nuclear cyclin D1, and Rb phosphorylation. EpCAM knockdown/overexpression in cancer cells, RT-PCR and Western blotting for cyclins, Rb phosphorylation assays, FHL2 co-depletion rescue experiments, immunohistochemistry of patient tissues Oncogene Medium 22391566
2013 EpCAM physically associates with claudin-7 (tight interaction) and, indirectly via claudin-7, with claudin-1, but not claudin-2 or claudin-4. This interaction stabilizes claudin-7 and claudin-1 by preventing their lysosomal degradation. EpCAM knockdown reduces claudin-7 and claudin-1 protein levels, which are restored by lysosomal inhibitors; this also paradoxically increases claudin accumulation at tight junctions and enhances transepithelial electroresistance. shRNA knockdown of EpCAM in T84 and Caco-2 cells, preparative immunoprecipitation, co-immunoprecipitation, co-transfection experiments, lysosomal inhibitor rescue, immunofluorescence microscopy, transepithelial electrical resistance measurement The Journal of biological chemistry High 23486470
2013 EpCAM acts as a potent inhibitor of novel protein kinase C (nPKC) through a short pseudosubstrate-like motif in its cytoplasmic tail that binds nPKCs with high affinity. Loss of EpCAM in amphibian embryos sequentially overstimulates PKC, activates the Erk pathway, exacerbates myosin contractility, disrupts cadherin-mediated adhesion, and causes tissue dissociation. This PKC-inhibitory mechanism is shared with other plasma membrane adhesion molecules. Loss-of-function in Xenopus embryos, PKC activity assays, Erk pathway measurements, myosin contractility readouts, in vitro binding assays of EpCAM cytoplasmic tail segment to nPKCs, bioinformatics motif analysis Developmental cell High 24183651
2000 GA733-2/EpCAM extracellular domain disulfide-bonding pattern was determined: cysteines 1–6 form a novel pattern (Cys1-Cys4, Cys2-Cys6, Cys3-Cys5) distinct from EGF-like structure, and cysteines 7–12 form a thyroglobulin type 1A pattern (Cys7-Cys8, Cys9-Cys10, Cys11-Cys12). N-linked glycosylation occurs at Asn88 (complete) and Asn51 (partial); Asn175 is not glycosylated; no O-linked carbohydrate was detected. MALDI mass spectrometry, N-terminal sequencing of tryptic peptides, chemical reduction and alkylation, glycosylation site analysis The Journal of biological chemistry High 11080501
2000 Full-length GA733-2/EpCAM exists as high-affinity non-covalent cis-dimers (Kd <10 nM for monomer-dimer) and lower-affinity tetramers (~10 µM for dimer-tetramer) in solution. The extracellular domain alone is monomeric. Cell-cell adhesion activity resides in the full-length dimer/tetramer; monomeric extracellular domain is inactive in cell aggregation inhibition assays. Sedimentation equilibrium ultracentrifugation, chemical cross-linking of purified protein and cells in suspension vs. monolayer, cell aggregation inhibition assay The Journal of biological chemistry High 11058587
2018 EpCAM monomers do not associate into intercellular homo-oligomers capable of mediating cell-cell adhesion. EpCAM forms stable cis-dimers on the surface of cells with pre-formed contacts (detected by FLIM-FRET), but no trans-oligomers between opposing cells were detectable. These findings argue against EpCAM functioning as a direct homophilic cell-cell adhesion molecule. SAXS, cross-linking mass spectrometry (XL-MS), bead aggregation assays, FLIM-FRET on cell surfaces Scientific reports High 30185875
2013 In a mouse model of congenital tufting enteropathy (CTE), deletion of EpCAM exon 4 causes mislocalization of residual mutant EpCAM protein, loss of claudin-7 colocalization, and disruption of the EpCAM/claudin-7 complex, leading to enhanced intestinal permeability and epithelial cell migration. These findings were confirmed in CTE patient intestinal tissue. Cre-LoxP mouse model (Epcam Δ4/Δ4), histology, light and electron microscopy, immunohistochemistry, permeability assays, co-localization studies in mouse and patient tissue American journal of physiology. Gastrointestinal and liver physiology High 24337010
2014 EpCAM mutation (exon 4 deletion) in intestinal epithelial cells leads to decreased electrical resistance, increased paracellular permeability, and decreased ion transport. In the inducible mouse model, EpCAM deficiency also decreases tight junctional protein expression in intestine. EpCAM shRNA knockdown in T84 colonic epithelial cells, transepithelial electrical resistance measurement, permeability assays, ion transport assays, tamoxifen-inducible EpCAM Δ4/Δ4 mouse model, Western blotting Journal of molecular medicine High 25482158
2020 The EGF-like domain I within the extracellular domain of EpCAM (EpEX) binds EGFR, activating AKT and MAPK signaling. AKT signaling inhibits FOXO3a and stabilizes PD-L1 protein; MAPK signaling also contributes to PD-L1 stabilization. Neutralizing EpCAM (anti-EpCAM antibody EpAb2-6) reduces PD-L1 levels and promotes FOXO3a nuclear translocation and HtrA2-mediated apoptosis. Co-immunoprecipitation of EpEX with EGFR, Western blotting for AKT/MAPK/FOXO3a/PD-L1, immunofluorescence for FOXO3a localization, in vivo mouse metastasis and orthotopic colorectal cancer models Cancer research Medium 32978170
2023 The extracellular domain of EpCAM (EpEX) binds HGFR (c-Met) and cooperates with HGF to activate downstream ERK and FAK-AKT signaling, stabilizes active β-catenin and Snail by reducing GSK3β activity, and promotes EMT and metastasis of colon cancer cells. Immunoprecipitation, ELISA, FRET to confirm EpEX-HGFR interaction, Western blotting for downstream signaling, cell proliferation/migration/invasion assays, tail-vein metastasis and orthotopic animal models Journal of translational medicine Medium 37543570
2013 EpCAM knockdown in breast cancer cells decreases NF-κB transcription factor activity (reduced RELA phosphorylation, increased IκBα) and reduces IL-8 expression. Rescue experiments show that RELA ablation or forced IκBα expression prevented EpCAM-dependent IL-8 promoter reactivation, placing EpCAM upstream of the NF-κB/RELA/IL-8 axis in breast cancer invasion. EpCAM siRNA knockdown in breast cancer cell lines, NF-κB reporter assays, RELA phosphorylation Western blotting, IκBα Western blotting, IL-8 ELISA, IL-1β stimulation, functional rescue with RELA siRNA and IκBα overexpression Molecular cancer research Medium 23378578
2019 EpCAM associates with integrin β1 (demonstrated by co-immunoprecipitation). EpCAM knockout (CRISPR/Cas9) in colorectal CW-2 and epidermoid A431 cells reduces integrin α5 expression, decreases FAK, AKT, and ERK phosphorylation, and impairs cell adhesion, migration, and colony formation. CRISPR/Cas9 knockout, co-immunoprecipitation, Western blotting for phospho-FAK/AKT/ERK, cell adhesion assays, migration assays, colony formation assays Biochemical and biophysical research communications Medium 31806375
2020 Matriptase cleaves both EpCAM and TROP2 in keratinocytes (HaCaT cells). Matriptase cleavage of EpCAM and TROP2 destabilizes claudin-1 and claudin-7 by routing them to lysosomes. This cleavage is inhibited by HAI proteins (HAI-1 more than HAI-2); dual knockdown of HAI-1 and HAI-2 causes near-complete cleavage of EpCAM/TROP2 and drastic reduction of claudins, reversible by concurrent matriptase knockdown. Protease-disabled matriptase or G827R mutant does not cleave EpCAM or TROP2. In vitro cleavage assay with purified recombinant proteins, co-transfection of matriptase in 293T cells, siRNA knockdown of HAI-1/HAI-2/matriptase in HaCaT cells, Western blotting, lysosomal inhibitor (chloroquine) rescue Cells High 32326212
2022 EPCAM and TROP2 share redundant roles in stabilizing claudin-7 at the cell membrane and in epithelial development across multiple tissues. TROP2 can compensate for loss of EPCAM in claudin-7 stabilization in tissues co-expressing both proteins; combined loss causes much more severe developmental defects than either single knockout alone. Epcam knockout mice, Trop2 knockout mice, Epcam/Trop2 double knockout mice, histology of multiple tissues, immunofluorescence for claudin-7 localization and expression, viability and growth tracking Biology open High 35730316
1994 DNA methylation of the TROP1/EpCAM gene locus prevents gene amplification after transfection. Demethylation of TROP1 (by 5-azacytidine treatment) allows efficient amplification of transfected TROP1 copies (up to 40 copies per haploid genome), demonstrating that methylation status controls the amplifiability of this locus. 5-azacytidine demethylation treatment of JAR choriocarcinoma cells, DNA transfection, FACS-based selection, Southern blot copy-number analysis, in vitro Sss I methylase treatment of DNA Proceedings of the National Academy of Sciences of the United States of America Medium 8016075
2003 Loss of TP53 (p53) induces demethylation of the TROP1/EpCAM gene, leading to TROP1 gene amplification. Reintroduction of wild-type TP53 into p53-null cells reverses the demethylation. In vitro methylation of transfected TROP1 DNA with Sss I methylase prevents amplification, establishing a p53→DNA methylation→TROP1 amplification axis. TP53 transfection into TP53-null cells, Southern blot for methylation and copy number, in vitro methylation with Sss I methylase, gene amplification assay in vivo Oncogene Medium 12642870
2015 An anti-EpCAM antibody (EpAb2-6) binding to positions Y95 and D96 of the EGF-II/TY domain of EpCAM inhibits production of EpICD, thereby decreasing its nuclear translocation and downstream signal activation (oncogenic signaling). This antibody induces cancer cell apoptosis in vitro and inhibits tumor growth in vivo. Antibody epitope mapping, Western blotting for EpICD production and nuclear translocation, cell apoptosis assays, xenograft mouse models Oncotarget Medium 26317650

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 569 19136966
1999 The biology of the 17-1A antigen (Ep-CAM). Journal of molecular medicine (Berlin, Germany) 467 10606205
2009 The emerging role of EpCAM in cancer and stem cell signaling. Cancer research 433 19584271
2007 EpCAM (CD326) finding its role in cancer. British journal of cancer 420 17211480
2020 Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years? Cancer metastasis reviews 268 32507912
2010 EpCAM in carcinogenesis: the good, the bad or the ugly. Carcinogenesis 257 20837599
2011 EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis. Journal of clinical pathology 236 21415054
2013 EpCAM: structure and function in health and disease. Biochimica et biophysica acta 229 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 158 18572020
2012 EpCAM and its potential role in tumor-initiating cells. Cell adhesion & migration 152 22647938
2008 CD44 and EpCAM: cancer-initiating cell markers. Current molecular medicine 149 19075676
2019 Biology and clinical relevance of EpCAM. Cell stress 146 31225512
2018 Functions of EpCAM in physiological processes and diseases (Review). International journal of molecular medicine 133 30015855
2003 EpCAM: A new therapeutic target for an old cancer antigen. Cancer biology & therapy 127 14508099
2013 Epithelial cell adhesion molecule (EpCAM) regulates claudin dynamics and tight junctions. The Journal of biological chemistry 112 23486470
2013 EPCAM deletion carriers constitute a unique subgroup of Lynch syndrome patients. Familial cancer 105 23264089
2012 EpCAM regulates cell cycle progression via control of cyclin D1 expression. Oncogene 99 22391566
2014 EpCAM and the biology of hepatic stem/progenitor cells. American journal of physiology. Gastrointestinal and liver physiology 98 25477371
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
2008 EpCAM expression in normal, non-pathological tissues. Frontiers in bioscience : a journal and virtual library 89 17981779
2018 Antibody Based EpCAM Targeted Therapy of Cancer, Review and Update. Current cancer drug targets 88 29295696
2014 Dynamic EpCAM expression on circulating and disseminating tumor cells: causes and consequences. Cellular and molecular life sciences : CMLS 87 25103341
2012 Significance of EpCAM and TROP2 expression in non-small cell lung cancer. World journal of surgical oncology 86 22482828
2020 Revisiting the Roles of Pro-Metastatic EpCAM in Cancer. Biomolecules 84 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
2022 Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside. Experimental hematology & oncology 76 36369033
2021 Functional Implications of the Dynamic Regulation of EpCAM during Epithelial-to-Mesenchymal Transition. Biomolecules 75 34209658
2013 Context-dependent adaption of EpCAM expression in early systemic esophageal cancer. Oncogene 73 24141784
2000 Determination of disulfide bond assignments and N-glycosylation sites of the human gastrointestinal carcinoma antigen GA733-2 (CO17-1A, EGP, KS1-4, KSA, and Ep-CAM). The Journal of biological chemistry 73 11080501
2018 EpCAMhigh and EpCAMlow circulating tumor cells in metastatic prostate and breast cancer patients. Oncotarget 68 30479699
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
2020 EpCAM Signaling Promotes Tumor Progression and Protein Stability of PD-L1 through the EGFR Pathway. Cancer research 64 32978170
2018 EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome. Human mutation 59 30461124
2009 EpCAM: another surface-to-nucleus missile. Cancer cell 58 19249674
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 56 33627408
2017 Relationship between epithelial cell adhesion molecule (EpCAM) overexpression and gastric cancer patients: A systematic review and meta-analysis. PloS one 51 28403178
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
2018 EpCAM Immunotherapy versus Specific Targeted Delivery of Drugs. Cancers 50 29329202
2013 EpCAM controls actomyosin contractility and cell adhesion by direct inhibition of PKC. Developmental cell 48 24183651
2000 Oligomeric state of the colon carcinoma-associated glycoprotein GA733-2 (Ep-CAM/EGP40) and its role in GA733-mediated homotypic cell-cell adhesion. The Journal of biological chemistry 45 11058587
2014 Expression of EpCAM(MF) and EpCAM(MT) variants in human carcinomas. Journal of clinical pathology 44 24465008
2013 Functional consequences of EpCam mutation in mice and men. American journal of physiology. Gastrointestinal and liver physiology 44 24337010
2016 EpCAM as multi-tumour target for near-infrared fluorescence guided surgery. BMC cancer 41 27842504
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
1994 DNA methylation prevents the amplification of TROP1, a tumor-associated cell surface antigen gene. Proceedings of the National Academy of Sciences of the United States of America 41 8016075
2014 Mutation of EpCAM leads to intestinal barrier and ion transport dysfunction. Journal of molecular medicine (Berlin, Germany) 40 25482158
2019 Shedding light on the EpCAM: An overview. Journal of cellular physiology 39 30628064
2014 Lynch-like syndrome: characterization and comparison with EPCAM deletion carriers. International journal of cancer 39 25110875
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
2015 The role of EpCAM in physiology and pathology of the epithelium. Histology and histopathology 36 26493939
2013 EpCAM-targeted therapy for human hepatocellular carcinoma. Annals of surgical oncology 35 24370904
2015 EpCAM Aptamer-siRNA Chimera Targets and Regress Epithelial Cancer. PloS one 34 26176230
2018 EpCAM homo-oligomerization is not the basis for its role in cell-cell adhesion. Scientific reports 33 30185875
2017 Selection and targeting of EpCAM protein by ssDNA aptamer. PloS one 33 29245156
2016 The plastic cellular states of liver cells: Are EpCAM and Lgr5 fit for purpose? Hepatology (Baltimore, Md.) 33 26799921
2013 Clinicopathologic implications of EpCAM and Sox2 expression in breast cancer. Clinical breast cancer 32 24201161
2020 Matriptase Cleaves EpCAM and TROP2 in Keratinocytes, Destabilizing Both Proteins and Associated Claudins. Cells 31 32326212
2013 EpCAM modulates NF-κB signaling and interleukin-8 expression in breast cancer. Molecular cancer research : MCR 31 23378578
2024 Regulation of the Function and Expression of EpCAM. Biomedicines 30 38791091
2017 EpCAM-based assays for epithelial tumor cell detection in cerebrospinal fluid. Journal of neuro-oncology 30 29192390
2003 Mutations of TP53 induce loss of DNA methylation and amplification of the TROP1 gene. Oncogene 30 12642870
2019 EpCAMlow Circulating Tumor Cells: Gold in the Waste. Disease markers 29 31636732
2017 EpCAM-expressing circulating tumor cells in colorectal cancer. The International journal of biological markers 29 28604994
2013 High EpCAM expression is linked to proliferation and lauren classification in gastric cancer. BMC research notes 29 23830302
2018 EpCAM duality becomes this molecule in a new Dr. Jekyll and Mr. Hyde tale. Critical reviews in oncology/hematology 28 29759567
2017 Cooverexpression of EpCAM and c-myc genes in malignant breast tumours. Journal of genetics 28 28360395
2016 EpCAM Inhibition Sensitizes Chemoresistant Leukemia to Immune Surveillance. Cancer research 28 27697766
2015 Expression of EpCAM and Wnt/ β-catenin in human colon cancer. Genetics and molecular research : GMR 28 25966221
2021 EpCAM-Mediated Cellular Plasticity Promotes Radiation Resistance and Metastasis in Breast Cancer. Frontiers in cell and developmental biology 26 33490064
2007 Trop-1 are conserved growth stimulatory molecules that mark early stages of tumor progression. Cancer 26 17559145
2022 Preclinical evaluation of [99mTc]Tc-labeled anti-EpCAM nanobody for EpCAM receptor expression imaging by immuno-SPECT/CT. European journal of nuclear medicine and molecular imaging 25 35013776
2015 Circulating tumor cells isolation: the "post-EpCAM era". Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 25 26543332
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
2015 Expression of epithelial cell adhesion molecule (EpCAM) in oral squamous cell carcinoma. Histopathology 24 26401964
2020 Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1. International journal of molecular sciences 23 32392820
2016 Expression of CEA, CA19-9, CA125, and EpCAM in pseudomyxoma peritonei. Human pathology 23 27038681
2022 EpCAM- and EGFR-Specific Antibody Drug Conjugates for Triple-Negative Breast Cancer Treatment. International journal of molecular sciences 22 35682800
2020 Current View on EpCAM Structural Biology. Cells 22 32486423
2014 Overexpression of EpCAM and Trop2 in pituitary adenomas. International journal of clinical and experimental pathology 22 25550831
2008 EpCAM in morphogenesis. Frontiers in bioscience : a journal and virtual library 21 18508569
2023 Epithelial cell adhesion molecule (EpCAM) regulates HGFR signaling to promote colon cancer progression and metastasis. Journal of translational medicine 20 37543570
2014 EpCAM, a potential therapeutic target for esophageal squamous cell carcinoma. Annals of surgical oncology 20 24566863
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
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
2022 EPCAM and TROP2 share a role in claudin stabilization and development of intestinal and extraintestinal epithelia in mice. Biology open 17 35730316
2018 Drug-induced expression of EpCAM contributes to therapy resistance in esophageal adenocarcinoma. Cellular oncology (Dordrecht, Netherlands) 17 30116994

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