Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?
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NON-THEMATIC REVIEW
Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years? Olivier Gires 1,2
&
Min Pan 1,3 & Henrik Schinke 1 & Martin Canis 1 & Patrick A. Baeuerle 4,5
# The Author(s) 2020
Abstract 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. Keywords EpCAM . Carcinoma . Metastasis . Regulatedintramembrane proteolysis . Liquid biopsy . Epithelial-to-mesenchymal transition
1 Introduction The epithelial cell adhesion molecule (EpCAM) has first been described in 1979 as a humoral antigen expressed on colon carcinoma cells [1]. Here, we have summarized the impressive * Olivier Gires [email protected] 1
Department of Otorhinolaryngology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
2
Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer”, Helmholtz Zentrum, Neuherberg, Germany
3
Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016, China
4
Institute for Immunology, LMU Munich, Grosshadernerstr. 9, 82152 Planegg, Martinsried, Germany
5
MPM Capital, Cambridge MA, 450 Kendall Street, Cambridge, MA 02142, USA
progress in the biology of EpCAM in the past four decades. Expression patterns, regulation, and the multiple functions of EpCAM in normal epithelia, in carcinoma, and in pluripotent stem cells are reviewed. Furthermore, the clinical implications and applications related to EpCAM are discussed. Lastly, the most recently discovered involvement of EpCAM in the regulation o
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