All together these data demonstrate that αvβ3-mediated adhesion of highly metastatic melanoma cells to its extracellular matrix substrate VN results in Src-dependent phosphorylation and up-regulation of p190RhoGAP activity, a Src-dependent decrease in RhoA activity and stress fiber and focal adhesion formation, and a Src-dependent increase in αvβ3-mediated invasion. The gene discussed is ARHGAP35; the disease is melanoma.