EpCAM: A Multifunctional Protein at the Crossroads of Cancer Biology, Diagnosis, and Immunotherapy

The cell surface protein of EpCAM (Epithelial Cell Adhesion Molecule), also known as CD326, is generally expressed in normal epithelia; whereas, its upregulation has been reported in certain tissue stem cells, precursors, and a number of epithelium-derived tumors. EpCAM was initially introduced as a transmembrane glycoprotein modulating cell-cell adhesion and facilitating epithelial-specific intercellular cell adhesion. However, its recognized functions have expanded to include diverse roles in fundamental cellular processes, such as the regulation of proliferation, differentiation, cell migration, and cell signaling. The aim of the current review is to unravel the mechanisms by which EpCAM controls the initiation of cancer through interaction and the formation of a complex with Wnt pathway molecules; also, to summarize and discuss the original data obtained from international research laboratories on the properties of EpCAM, including its exclusive expression in human CSCs (Cancer Stem Cells) and CTCs (Circulating Tumor Cells). Questions on this topic, such as how this property led to this molecule being considered a diagnostic and prognostic agent for the detection and monitoring of various carcinomas, are also addressed. This review provides the significance of EpCAM-based identification in liquid biopsy and describes its clinical applications in targeted therapeutic approaches. We also discuss on EpCAM-targeted therapeutic approaches, including monoclonal antibodies, CAR-T cells, and bispecific antibodies. In conclusion, we discuss future research directions in which EpCAM targeting could contribute to further progress in cancer diagnosis, prognosis, and treatment.