P120ctn supports E-cadherin-mediated reversion of the invasive phenotype of pancreatic carcinoma cells

The extraordinary high number of metastases in pancreatic cancer prompted us to analyse the relevance of E-Cadherin for cellular adhesion in human pancreatic carcinoma. E-cadherin represents the predominant cell-cell adhesion molecule in epithelial cells. The main function of E-cadherin is establishment and maintenance of cell-cell adhesion and tissue integrity. Ecadherin deficiency is a feature of most invasive carcinomas, which characterises E-cadherin as a suppressor of invasion (Frixen et al. 1991). Inside the cell cadherin is associated with the actin cytoskeleton by different catenins, namely - and -catenin. The catenin p120 associates directly with cadherins, the binding site is located in the cadherin juxtamembrane domain and differs from that of -catenin (Yap et al. 1998). Regulation of lateral clustering of cadherin molecules is discussed as a mechanism by which p120ctn influence E-cadherin-mediated cellcell adhesion. For re-expression of E-cadherin, we choose the pancreatic carcinoma cell line MIA PaCa-2 because these cells do not express E-cadherin, show reduced levels of - and catenin and are characterised by a high metasta tic potential. Conclusions: - Re-expression of E-cadherin is sufficient to inhibit invasive growth of pancreatic carcinoma cells in vivo; - The presence of P-cadherin or the e xpression of N-cadherin does not result in increased cell aggregation and suppression of invasion - Catenin p120 is bound to all three cadherins analysed here - Loss of p120ctn phosphorylation correlates with a functional cadherin/catenin adhesion complex and suppression of invasion.