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

Abstract

E‐cadherin is a transmembrane protein that mediates Ca²⁺‐dependent cell‐cell adhesion and is implicated in a number of biologic processes, including cell growth and differentiation, cell recognition and cell sorting during development. 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 the E‐cadherin/catenin system. We demonstrate that both FGF‐1 and FGF‐2 upregulate E‐cadherin and β‐catenin at the protein level in the BxPc3 and HPAF cell lines and modestly in T3M4 cells. FGF‐1 and FGF‐2 facilitate the association of E‐cadherin and α‐catenin with the cytoskeleton, as demonstrated 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 that FGF‐1 and FGF‐2 contribute to the integrity and thus the function of the complex. Furthermore, FGFs facilitate the assembly of the E‐cadherin/catenin axis. The effect is associated with elevation of tyrosine phosphorylation of E‐cadherin, α‐catenin, β‐4051μcatenin and γ‐catenin, but not p120^ctn. These findings indicate that the E‐cadherin/catenin system is a target of the FGF/FGFR system and that coordinated signals from both systems may determine the ultimate biologic responses.