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-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.
El-Hariry
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I
Imperial Cancer Research Fund Molecular Oncology Unit, Imperial College School of Medicine, Hammersmith Campus, London, United Kingdom.
Pignatelli
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M
Lemoine
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NR
D000230:Adenocarcinoma / Q000378:metabolism*; D015820:Cadherins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D002450:Cell Communication; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D014443:Tyrosine