INSULIN-LIKE GROWTH-FACTORS AS REGULATORS OF CELL MOTILITY - SIGNALING MECHANISMS

Accumulating evidence indicates that the insulin-like growth factors ( IGFs) function not only as mitogenic factors, but also as promoters of cell motility. In this article we review the current knowledge concer ning the biochemical mechanisms whereby the IGFs activate cell motilit y. A key aspect of IGF-stimulated cell motility is the ability of IGFs to promote actin polymerization at the leading edge of the cell. This effect of the IGFs is mediated by activation and autophosphorylation of the type IIGF receptor followed by docking of insulin receptor subs trate-1 (IRS-1), stimulation of phosphatidylinositol (PI) 3-kinase, an d possibly activation of the small GTPase Rac. IGF-stimulated cell mot ility also requires the formation of new adhesions, a process associat ed with tyrosine phosphorylation of paxillin and focal adhesion kinase . Determining the biochemical mechanisms by which IGFs regulate cell m otility should allow for a better understanding of bone remodeling, ne urite outgrowth, tumor metastasis, placental formation, and Skin and b lood vessel repair. (C) 1997, Elsevier Science Inc.