Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?
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Published:2020-06-07
Issue:3
Volume:39
Page:969-987
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ISSN:0167-7659
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Container-title:Cancer and Metastasis Reviews
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language:en
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Short-container-title:Cancer Metastasis Rev
Author:
Gires OlivierORCID, Pan Min, Schinke Henrik, Canis Martin, Baeuerle Patrick A.
Abstract
AbstractEpCAM (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.
Funder
Deutsche Forschungsgemeinschaft Bayerisches Staatsministerium für Wirtschaft und Medien, Energie und Technologie
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
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