Autotaxin promotes motility via G protein-coupled phosphoinositide 3-kinase gamma in human melanoma cells

Abstract

Autotaxin (ATX), an exo-nucleotide pyrophosphatase and phosphodiesterase, stimulates tumor cell motility at subnanomolar levels and augments invasiveness and angiogenesis. We investigated the role of G protein-coupled phosphoinositide 3-kinase gamma (P13Kgamma) in ATX-mediated tumor cell motility stimulation. Pretreatment of human melanoma cell line A2058 with wortmannin or LY294002 inhibited ATX-induced motility. ATX increased the P13K activity in p110gamma, but not p85, immunoprecipitates. This effect was abrogated by P13K inhibitors or inhibited by pertussis toxin. Furthermore, stimulation of tumor cell motility by ATX was inhibited by catalytically inactive form of PI3Kgamma, strongly indicating the crucial role of PI3Kgamma for ATX-mediated motility in human melanoma cells. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.