E-cadherin is the main cell–cell adhesion molecule in epithelial tissues and is regarded as a master organizer of the epithelial phenotype (Takeichi, 1995). Direct mutation of the E-cadherin gene in gastric and lobular breast carcinomas indicates a classical tumor suppressor role in some tumors (Oda et al., 1994; Berx et al., 1995). In late-stage carcinomas of all types, E-cadherin down-regulation occurs frequently via epigenetic mechanisms (Comijn et al., 2001; Matsumura et al., 2001) and is closely correlated with the transition to metastasis (Frixen et al., 1991; Vleminckx et al., 1991; Birchmeier and Behrens, 1994; Perl et al., 1998). Together, these data establish E-cadherin as a tumor and/or metastasis suppressor, depending on the mechanism and timing of E-cadherin down-regulation (for review see Yap, 1998; Nollet et al., 1999).
