EpCAM, the Epithelial Cell Adhesion Molecule, is a well-known type I transmembrane glycoprotein. It was initially discovered as a tumor antigen on colorectal carcinomas. Despite its name suggesting a cell adhesion role, it has various functions. It is involved in regulating cell adhesion, proliferation, migration, stemness, and epithelial-to-mesenchymal transition (EMT) of carcinoma cells. It interacts with multiple molecules like claudins, CD44, E-cadherin, EGFR, and components of the WNT and Ras/Raf pathways, playing an essential role in embryonic morphogenesis, intestinal homeostasis, and having a strong correlation with cancer prognosis [1,3]. Genetic animal models are useful for understanding its in-vivo functions [5].

EpCAM is highly expressed in carcinomas, and its expression is associated with poor cancer prognosis. In hepatocellular carcinoma (HCC), EpCAM-high liver cancer stem cells resist natural killer cell-mediated cytotoxicity by upregulating CEACAM1 [2]. It has also been shown to repress myosin contractility through a PKC signaling cascade, conferring the property of favoring tissue plasticity [1]. Additionally, it may play a role in cell-cell adhesion and migration, with its function potentially involving the inhibition of novel PKC family members and a specific downstream PKD-Erk cascade [4].

In conclusion, EpCAM is a multi-functional protein involved in key biological processes such as cell adhesion, migration, and proliferation. Its overexpression in carcinomas and role in cancer-related processes like metastasis and resistance to immune cell-mediated cytotoxicity highlight its importance in cancer research. The use of genetic models has provided insights into its functions in physiological and disease conditions, especially in cancer, helping to understand its complex role in carcinogenesis and potentially leading to new diagnostic and therapeutic strategies.