Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?

EpCAM (epithelial cell adhesion molecule) was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression on carcinomas and their metastases, EpCAM serves as a prognostic marker, a therapeutic target, and an anchor molecule on circulating and di...

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Published in:Cancer and metastasis reviews Vol. 39; no. 3; pp. 969 - 987
Main Authors: Gires, Olivier, Pan, Min, Schinke, Henrik, Canis, Martin, Baeuerle, Patrick A.
Format: Journal Article
Language:English
Published: New York Springer US 01.09.2020
Springer
Springer Nature B.V
Subjects:
Animals
Antigens
Biomedical and Life Sciences
Biomedicine
Cancer Research
CD44 antigen
Cell adhesion & migration
Cell adhesion molecules
Cell migration
Cell proliferation
Colorectal cancer
Colorectal carcinoma
E-cadherin
Epidermal growth factor
Epidermal growth factor receptors
Epithelial Cell Adhesion Molecule - biosynthesis
Epithelial Cell Adhesion Molecule - metabolism
Epithelial cells
Epithelial-Mesenchymal Transition
Health aspects
Humans
Intracellular
Intracellular signalling
Mesenchyme
Metastases
Metastasis
Neoplasms - metabolism
Neoplasms - pathology
Non-Thematic Review
Oncology
Proteolysis
Raf protein
Stem cells
Tumor cells
Wnt protein
Liquid biopsy
Carcinoma
Metastasis
EpCAM
Regulated intramembrane proteolysis
Epithelial-to-mesenchymal transition
ISSN:0167-7659, 1573-7233, 1573-7233
Online Access:Get full text
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Summary:EpCAM (epithelial cell adhesion molecule) was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression on carcinomas and their metastases, EpCAM serves as a prognostic marker, a therapeutic target, and an anchor molecule on circulating and disseminated tumor cells (CTCs/DTCs), which are considered the major source for metastatic cancer cells. Today, EpCAM is reckoned as a multi-functional transmembrane protein involved in the regulation of cell adhesion, proliferation, migration, stemness, and epithelial-to-mesenchymal transition (EMT) of carcinoma cells. To fulfill these functions, EpCAM is instrumental in intra- and intercellular signaling as a full-length molecule and following regulated intramembrane proteolysis, generating functionally active extra- and intracellular fragments. Intact EpCAM and its proteolytic fragments interact with claudins, CD44, E-cadherin, epidermal growth factor receptor (EGFR), and intracellular signaling components of the WNT and Ras/Raf pathways, respectively. This plethora of functions contributes to shaping intratumor heterogeneity and partial EMT, which are major determinants of the clinical outcome of carcinoma patients. EpCAM represents a marker for the epithelial status of primary and systemic tumor cells and emerges as a measure for the metastatic capacity of CTCs. Consequentially, EpCAM has reclaimed potential as a prognostic marker and target on primary and systemic tumor cells.
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ISSN:0167-7659
1573-7233
1573-7233
DOI:10.1007/s10555-020-09898-3