The α6β4 integrin and epithelial cell migration

Although the involvement of alpha6 beta4, an integrin laminin receptor, in hemidesmosome organization has dominated the study of this integrin, recent studies are revealing novel functions for alpha6 beta4 in the migration of epithelial and carcinoma cells. The engagement of laminin by alpha6 beta4 can stabilize actin-rich protrusions and mediate traction forces necessary for cell movement. This integrin also has a significant impact on signaling molecules that stimulate migration and invasion, especially PI3-K and Rho GTPases. Activation of PI3-K by alpha6 beta4 enhances the formation of actin protrusions, and it may stimulate the function of other integrins, such as alpha3 beta1, that are also important for epithelial migration. Signaling through alpha6 beta4 may not always depend on the adhesive functions of this integrin, a possibility that has profound implications for migration and invasion because it implies that the ability of alpha6 beta4 to stimulate these processes is not limited to specific matrix environments.