A Novel Mechanism of Crosstalk between Fibroblast Growth Factor Receptor and Integrin alphav beta3

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We previously reported that Fibroblast growth factor 1 (FGF1) binds both FGF receptor and integrin avb3, and also reported that integrin binding defective FGF1 mutant (Arg 50 to Glu, R50E) is defective in a fibroblast cell proliferation and migration. In this study, we tested if the interaction between FGF1 and integrin avb3 is required for angiogenesis and tumor growth. Here we demonstrated that FGF1-R50E is defective in inducing endothelial cell migration and tube formation, and suppressed wild-type FGF1-induced signaling (dominant-negative effect) in vitro. FGF1-R50E suppressed growth of colon cancer cells which subcutaneously transplanted in nude mice. These findings suggest that FGFR and integrin avb3 crosstalk through direct integrin binding to FGF, and that R50E acts as an antagonist to FGFR. We proposed that FGF1-R50E has potential as an anti-angiogenesis and anti-cancer therapeutic.