Integrin α 3 β 1 directs the stabilization of a polarized lamellipodium in epithelial cells through activation of Rac 1

Cell migration is a crucial event that occurs during many processes including wound healing, angiogenesis, development and metastasis. Although migratory phenotypes and factors that promote migration vary greatly among cell types, the basic mechanism that drives cell migration in all cells is polarized actin polymerization (Pollard and Borisy, 2003). This process is initiated by chemotactic factors that stimulate localized actin polymerization and the formation of an initial protrusion. Adhesion to an extracellular matrix (ECM) is not required for formation of these initial protrusions, as demonstrated by the fact that cells in suspension extend protrusions in response to growth factor stimulation. However, these initial protrusions are never as large as the lamellipodia that form when cells are plated onto adhesive substrates, suggesting an important role for adhesion in promoting the formation of stable leading-edge lamellipodia (Bailly et al., 1998). Integrins are the major cell surface receptors for cell adhesion to the ECM and they are known to play an important role in cell migration (Hynes, 2002; Ridley et al., 2003). Several integrins have been shown to localize to leading-edge lamellipodia in migrating cells, including α5β1 in fibroblasts