The tumor antigen EpCAM: tetraspanins and the tight junction protein claudin-7, new partners, new functions.

The cell-cell adhesion molecule EpCAM/CD326 has been one of the first tumor-associated antigens and has soon received attention as an antibody target in cancer therapy. However, only recently, progress has been achieved in disclosing the array of functional activities of EpCAM and the underlying molecular mechanisms. This review will particularly focus on cooperative activity of EpCAM with two classes of transmembrane molecules, tetraspanins and claudins. EpCAM can associate with claudin-7 and the tetraspanins CD9 and CO-029. We propose that complex formation of EpCAM with tetraspanins and claudins does not only interfere with EpCAM-mediated homotypic cell-cell adhesion, but importantly, is also associated with a gain of function, like induction of apoptosis resistance.