%0 Journal Article
%T Crosstalk between Fibroblast Growth Factor (FGF) Receptor and Integrin through Direct Integrin Binding to FGF and Resulting Integrin-FGF-FGFR Ternary Complex Formation
%A Seiji Mori
%A Yoshikazu Takada
%J Medical Sciences
%D 2013
%R 10.3390/medsci1010020
%X Fibroblast growth factors (FGFs) play a critical role in diverse physiological processes and the pathogenesis of diseases. Integrins are involved in FGF signaling, since integrin antagonists suppress FGF signaling. This is called integrin-FGF crosstalk, while the specifics of the crosstalk are unclear. This review highlights recent findings that FGF1 directly interacts with integrin ¦Áv¦Â3, and the resulting integrin-FGF-fibroblast growth factor receptor (FGFR) ternary complex formation is essential for FGF1-induced cell proliferation, migration and angiogenesis. An integrin-binding defective FGF1 mutant (Arg-50 to Glu, R50E) is defective in ternary complex formation and in inducing cell proliferation, migration and angiogenesis, while R50E still binds to the FGF receptor and heparin. In addition, R50E suppressed tumorigenesis in vivo, while wild-type (WT) FGF1 enhanced it. Thus, the direct interaction between FGF1 and integrin ¦Áv¦Â3 is a potential therapeutic target, and R50E is a potential therapeutic agent.
%K FGF1
%K integrin
%K crosstalk
%K dominant-negative mutant
%U http://www.mdpi.com/2076-3271/1/1/20