Receptor tyrosine kinase signaling required for integrin αvβ5-directed cell motility but not adhesion on vitronectin

Abstract

FG human pancreatic carcinoma cells adhere to vitronectin using integrin αvβ5 yet are unable to migrate on this ligand whereas they readily migrate on collagen in an α2β1-dependent manner. We report here that epidermal growth factor receptor (EGFR) activation leads to de novo αvβ5-dependent FG cell migration on vitronectin. The EGFR specific tyrosine kinase inhibitor tyrphostin 25 selectively prevents EGFR autophosphorylation thereby preventing the EGF-induced FG cell migration response on vitronectin without affecting constitutive migration on collagen. Protein kinase C (PKC) activation also leads to αvβ5-directed motility on vitronectin; however, this is not blocked by tyrosine kinase inhibitors. In this case, PKC activation appears to be associated with and downstream of EGFR signaling since calphostin C, an inhibitor of PKC, blocks FG cell migration on vitronectin induced by either PKC or EGF. These findings represent the first report implicating a receptor tyrosine kinase in a specific integrin mediated cell motility event independent of adhesion.