Schematic representation of signaling pathways involving EPCAM , proposed by Maetzel D et al. (2009). (a) Cleavage of EPCAM by TACE and PS-2. (b) EPCAM signalling and possible cross-talk with E-cadherin and Wnt pathways. EPCAM signalling is induced by RIP, leading to EpICD nuclear translocation in a complex with FHL2 and -catenin. Within the nucleus, the EpICD complex interacts with Lef-1 and contacts DNA. Upon interference with E-cadherin, EPCAM may increase the availability of its interaction partner -catenin in the soluble fraction. Cross-talk with the Wnt pathway is conceivable at the level of -catenin and Lef-1 interactions with EpICD, and is known for induction of the EPCAM promoter by Tcf4 (Maetzel D, Denzel S, Mack B, et al., Nature Cell Biology 11, 162 – 171, 2009).