The alpha 6 beta 4 integrin and epithelial cell migration.
Although the involvement of alpha 6 beta 4, an integrin laminin receptor, in hemidesmosome organization has dominated the study of this integrin, recent studies are revealing novel functions for alpha 6 beta 4 in the migration of epithelial and carcinoma cells. The engagement of laminin by alpha 6 beta 4 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 alpha 6 beta 4 enhances the formation of actin protrusions, and it may stimulate the function of other integrins, such as alpha 3 beta 1, that are also important for epithelial migration. Signaling through alpha 6 beta 4 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 alpha 6 beta 4 to stimulate these processes is not limited to specific matrix environments.
Mercurio
A M
AM
Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02115, USA. amercuri@caregroup.harvard.edu
Rabinovitz
I
I
Shaw
L M
LM
D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000502:physiology*; D002277:Carcinoma / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D004847:Epithelial Cells / Q000502:physiology*; D022002:Hemidesmosomes / Q000378:metabolism; D039161:Integrin alpha6beta4; D016023:Integrins / Q000737:chemistry / Q000502:physiology*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
D000954:Antigens, Surface; D039161:Integrin alpha6beta4; D016023:Integrins