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

• 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
• DOI: 10.1007/s10555-020-09898-3

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.