Extracellular FGF-1 inhibits cytoskeletal organization and promotes fibroblast motility

Previous efforts from this laboratory have established that acidic fibroblast growth factor (FGF-1), either added exogenously or secreted as a biologically active protein, induces a transformed phenotype in primary murine fibroblasts. Experimental studies described here demonstrate that constitutive exposure to extracellular FGF-1 results in reduced cell attachment to multiple ligands, inhibition of cytoskeletal organization, and reduced collagen contraction, despite no detectable change in integrin cell surface expression. In addition, FGF-1-transduced fibroblasts demonstrated a > 10-fold increase in migration, an observation correlated with increased tyrosine phosphorylation of p125FAK and p130CAS, Collectively, these results suggest that FGF-1-induced fibroblast transformation includes the involvement of specific FGF receptor-mediated signal transduction cascades targeted to cytoskeletal and focal adhesion structures.