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

Int J Cancer. 2001 Dec 1;94(5):652-61. doi: 10.1002/ijc.1515.


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 beta-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 alpha-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, alpha-catenin, beta-4051 mu-catenin and gamma-catenin, but not p120ctn. 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.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Cadherins / analysis*
  • Cadherins / chemistry
  • Cadherins / metabolism
  • Cell Communication
  • Cytoskeletal Proteins / analysis*
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / metabolism
  • Fibroblast Growth Factor 1 / pharmacology*
  • Fibroblast Growth Factor 2 / pharmacology*
  • Humans
  • Pancreatic Neoplasms / metabolism*
  • Phosphorylation
  • Trans-Activators*
  • Tumor Cells, Cultured
  • Tyrosine / metabolism
  • alpha Catenin
  • beta Catenin


  • CTNNA1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Trans-Activators
  • alpha Catenin
  • beta Catenin
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 1
  • Tyrosine