Finally, several lines of evidence suggest that this new role for p120 in regulating cadherin turnover may be important in cancer. In cell lines, E-cadherin loss leaves p120 stranded in the cytoplasm, but has little effect on p120 levels. It is well established that E-cadherin loss occurs frequently by mutation (Berx et al., 1998) and by epigenetic mechanisms (Comijn et al., 2001; Matsumura et al., 2001) that probably do not involve p120. In contrast, p120 loss clearly represents a different scenario that directly induces loss of E-cadherin, and thus ultimately, the entire cadherin complex. It follows that p120 loss may precede cadherin loss in the reported subset of tumors that have been shown to lack both proteins (for review see Thoreson and Reynolds, 2002). Accumulating evidence suggests that p120 down-regulation occurs frequently in colon, prostate, lung, bladder, breast, and several other malignancies (for review see Thoreson and Reynolds, 2002). p120 is both mutated and underexpressed in the colon carcinoma cell line SW48, and indeed, E-cadherin is indeed strongly down-regulated in these cells, providing the first physiologically relevant example of this
