ArticlePLoS biology2018
EpCAM ectodomain EpEX is a ligand of EGFR that counteracts EGF-mediated epithelial-mesenchymal transition through modulation of phospho-ERK1/2 in head and neck cancers.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Association of Epithelial to Mesenchymal transition Markers on Prognosis and Clinicopathological Characteristics in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.Head and neck pathology · 2025Pooled it
- Gene dependency-informed inference of response to targeted cancer therapies.Nature communications · 2026Article
- EpCAM supports exit from pluripotency of embryonic stem cells via Eomes.Cell death & disease · 2026Article
- Functional effects of EpCAM N-glycosylation in MDA-MB-468 breast cancer cells.Scientific reports · 2026Article
- Circulating Tumor Cells Detected Using EpAb3-5 as Prognostic Indicators in Head and Neck Squamous Cell Carcinoma.Journal of Cancer · 2026Article
- EpCAM activates the ERK-EGR1 signaling axis and promotes TNF-α-induced the progression of anaplastic thyroid cancer.Journal of translational medicine · 2025Article
- Circulating Tumor Cells in Head and Neck Squamous-Cell Carcinoma Exhibit Distinct Properties Based on Targeted Epithelial-Related Markers.Current issues in molecular biology · 2025Article
- EGFR-mediated local invasiveness and response to Cetuximab in head and neck cancer.Molecular cancer · 2025Article
- Characterization of EpCAM-Positive and EpCAM-Negative Tumor Cells in Early-Stage Breast Cancer.International journal of molecular sciences · 2024Article
- Intracellular domain of epithelial cell adhesion molecule induces Wnt receptor transcription to promote colorectal cancer progression.Journal of biomedical science · 2024Article
- Characterization of EpCAM in thyroid cancer biology by three-dimensional spheroids in vitro model.Cancer cell international · 2024Article
- Regulation of the Function and Expression of EpCAM.Biomedicines · 2024Review
- Resistance of HNSCC cell models to pan-FGFR inhibition depends on the EMT phenotype associating with clinical outcome.Molecular cancer · 2024Article
- Nature's Elixir for Cancer Treatment: Targeting Tumor-induced Neovascularization.Current medicinal chemistry · 2024Review
- EpCAM tumor specificity and proteoform patterns in urothelial cancer.Journal of cancer research and clinical oncology · 2023Article
- 5'-Ectonucleotidase CD73/NT5E supports EGFR-mediated invasion of HPV-negative head and neck carcinoma cells.Journal of biomedical science · 2023Article
- GINS4 suppresses ferroptosis by antagonizing p53 acetylation with Snail.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside.Experimental hematology & oncology · 2022Review
- A transcriptomic map of EGFR-induced epithelial-to-mesenchymal transition identifies prognostic and therapeutic targets for head and neck cancer.Molecular cancer · 2022Article
- Ep-CAM (MOC-31) expression in tooth germ and ameloblastoma.Medicina oral, patologia oral y cirugia bucal · 2022Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Head and neck squamous cell carcinomas (HNSCCs) are characterized by outstanding molecular heterogeneity that results in severe therapy resistance and poor clinical outcome. Inter- and intratumoral heterogeneity in epithelial-mesenchymal transition (EMT) was recently revealed as a major parameter of poor clinical outcome. Here, we addressed the expression and function of the therapeutic target epidermal growth factor receptor (EGFR) and of the major determinant of epithelial differentiation epithelial cell adhesion molecule (EpCAM) in clinical samples and in vitro models of HNSCCs. We describe improved survival of EGFRlow/EpCAMhigh HNSCC patients (n = 180) and provide a molecular basis for the observed disparities in clinical outcome. EGF/EGFR have concentration-dependent dual capacities as inducers of proliferation and EMT through differential activation of the central molecular switch phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) and EMT transcription factors (EMT-TFs) Snail, zinc finger E-box-binding homeobox 1 (Zeb1), and Slug. Furthermore, soluble ectodomain of EpCAM (EpEX) was identified as a ligand of EGFR that activates pERK1/2 and phosphorylated AKT (pAKT) and induces EGFR-dependent proliferation but represses EGF-mediated EMT, Snail, Zeb1, and Slug activation and cell migration. EMT repression by EpEX is realized through competitive modulation of pERK1/2 activation strength and inhibition of EMT-TFs, which is reflected in levels of pERK1/2 and its target Slug in clinical samples. Accordingly, high expression of pERK1/2 and/or Slug predicted poor outcome of HNSCCs. Hence, EpEX is a ligand of EGFR that induces proliferation but counteracts EMT mediated by the EGF/EGFR/pERK1/2 axis. Therefore, the emerging EGFR/EpCAM molecular cross talk represents a promising target to improve patient-tailored adjuvant treatment of HNSCCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.