EpCAM cellular functions in adhesion and migration, and potential impact on invasion: A critical review

EpCAM has long been known as a cell surface protein highly expressed in carcinomas. It has since become one of the key cancer biomarkers. Despite its high fame, its actual role in cancer development is still controversial. Beyond a flurry of correlative studies, which point either to a positive or a negative link with tumour progression, there has been surprisingly few studies on the actual cellular mechanisms of EpCAM and on their functional consequences. Clearly, EpCAM plays multiple important roles, in cell proliferation as well as in cell adhesion and migration. The two latter functions, directly relevant for metastasis, are the focus of this review. We attempt here to bring together the available experimental data to build a global coherent view of EpCAM functions. We also include in this overview EpCAM2/Trop2, the close relative of EpCAM. At the core of EpCAM (and EpCAM2/Trop2) function stands the ability to repress contractility of the actomyosin cell cortex. This activity appears to involve direct inhibition by EpCAM of members of the novel PKC family and of a specific downstream PKD-Erk cascade. We will discuss how this activity can result in a variety of adhesive and migratory phenotypes, thus potentially explaining at least part of the apparent inconsistencies between different studies. The picture remains fragmented, and we will highlight some of the conflicting evidence and the many unsolved issues, starting with the controversy around its original description as a cell-cell adhesion molecule.