FGF-1 and FGF-2 regulate the expression of E-cadherin and catenins in pancreatic adenocarcinoma

E-cadherin is a transmembrane protein that mediates Ca2+-dependent cell-cel l adhesion and is implicated in a number of biologic processes, including c ell growth and differentiation, cell recognition and cell sorting during de velopment. We have previously demonstrated that both cell-cell adhesion and invasion are modulated by fibroblast growth factor (FGF)-1 and FGF-2 in a panel of pancreatic adenocarcinoma cell lines (BxPc3, T3M4 and HPAF). Here, we examine further the role of FGFs in the expression and activation of th e E-cadherin/catenin system. We demonstrate that both FGF-1 and FGF-2 upreg ulate E-cadherin and beta -catenin at the protein level in the BxPc3 and HP AF cell lines and modestly in T3M4 cells. FGF-I and FGF-2 facilitate the as sociation of E-cadherin and alpha -catenin with the cytoskeleton, as demons trated by the increase in the detergent-insoluble fraction of E-cadherin in BxPc3 and HPAF cells. Since the correct function of the E-cadherin/catenin complex requires its association with the cytoskeleton, our data suggest t hat FGF-1 and FGF-2 contribute to the integrity and thus the function of th e complex. Furthermore, FGFs facilitate the assembly of the E-cadherin/cate nin axis. The effect is associated with elevation of tyrosine phosphorylati on of E-cadherin, alpha -catenin, beta -4051 mu catenin and gamma -catenin, but not p120(ctn). These findings indicate that the E-cadherin/catenin sys tem is a target of the FGF/FGFR system and that coordinated signals from bo th systems may determine the ultimate biologic responses. (C) 2001 Wiley-Li ss, Inc.