In the event of E-cadherin down-regulation, α- and β-catenins are rapidly degraded (Nagafuchi et al., 1991) via an adenomatous polyposis coli–dependent mechanism (Polakis, 2000) that ultimately targets β-catenin for destruction by the proteosome (for review see Kikuchi, 2000). In contrast, p120 is stable in the absence of cadherins and becomes stranded in the cytoplasm (Thoreson et al., 2000). Ourselves and others have postulated that cytoplasmic p120 actively drives the metastatic phenotype in cadherin-deficient cells through inappropriate activation/suppression of various Rho-GTPases such as Rac1 and RhoA (Anastasiadis et al., 2000; Noren et al., 2000; Anastasiadis and Reynolds, 2001; Grosheva et al., 2001). These data suggest a metastasis promoter role for p120 when mislocalized through prior loss of E-cadherin.
