ArticleThe Journal of biological chemistry2015
Cleavage and cell adhesion properties of human epithelial cell adhesion molecule (HEPCAM).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Clinicopathological and prognostic value of epithelial cell adhesion molecule in solid tumours: a meta-analysis.Frontiers in oncology · 2023Pooled it
- Trop-1/EpCAM Thr115 is a driver of hyperproliferative cell repair and of severe lung damage in COVID-19.iScience · 2026Article
- Article
- EpCAM activates the ERK-EGR1 signaling axis and promotes TNF-α-induced the progression of anaplastic thyroid cancer.Journal of translational medicine · 2025Article
- Intracellular domain of epithelial cell adhesion molecule induces Wnt receptor transcription to promote colorectal cancer progression.Journal of biomedical science · 2024Article
- Regulation of the Function and Expression of EpCAM.Biomedicines · 2024Review
- TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2).Atherosclerosis plus · 2022Article
- Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside.Experimental hematology & oncology · 2022Review
- EPCAM and TROP2 share a role in claudin stabilization and development of intestinal and extraintestinal epithelia in mice.Biology open · 2022Article
- CRISPR/Cas9 disruption of EpCAM Exon 2 results in cell-surface expression of a truncated protein targeted by an EpCAM specific T cell engager.Biochemistry and biophysics reports · 2022Article
- Article
- Trop2 Forms a Stable Dimer with Significant Structural Differences within the Membrane-Distal Region as Compared to EpCAM.International journal of molecular sciences · 2021Article
- Evolution of Thyroglobulin Loop Kinetics in EpCAM.Life (Basel, Switzerland) · 2021Article
- Digital scoring of EpCAM and slug expression as prognostic markers in head and neck squamous cell carcinomas.Molecular oncology · 2021Article
- Destabilization of EpCAM dimer is associated with increased susceptibility towards cleavage by TACE.PeerJ · 2021Article
- Article
- EpCAM as Modulator of Tissue Plasticity.Cells · 2020Review
- Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?Cancer metastasis reviews · 2020Review
- Current View on EpCAM Structural Biology.Cells · 2020Review
- Revisiting the Roles of Pro-Metastatic EpCAM in Cancer.Biomolecules · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human epithelial cell adhesion molecule (HEPCAM) is a tumor-associated antigen frequently expressed in carcinomas, which promotes proliferation after regulated intramembrane proteolysis. Here, we describe extracellular shedding of HEPCAM at two α-sites through a disintegrin and metalloprotease (ADAM) and at one β-site through BACE1. Transmembrane cleavage by γ-secretase occurs at three γ-sites to generate extracellular Aβ-like fragments and at two ϵ-sites to release human EPCAM intracellular domain HEPICD, which is efficiently degraded by the proteasome. Mapping of cleavage sites onto three-dimensional structures of HEPEX cis-dimer predicted conditional availability of α- and β-sites. Endocytosis of HEPCAM warrants acidification in cytoplasmic vesicles to dissociate protein cis-dimers required for cleavage by BACE1 at low pH values. Intramembrane cleavage sites are accessible and not part of the structurally important transmembrane helix dimer crossing region. Surprisingly, neither chemical inhibition of cleavage nor cellular knock-out of HEPCAM using CRISPR-Cas9 technology impacted the adhesion of carcinoma cell lines. Hence, a direct function of HEPCAM as an adhesion molecule in carcinoma cells is not supported and appears to be questionable.
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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.