Integrin α₆β₄ cooperates with LPA signaling to stimulate Rac through AKAP-Lbc-mediated RhoA activation

Abstract

O'Connor KL, Chen M, Towers LN. Integrin ␣6␤4 cooperates with LPA signaling to stimulate Rac through AKAP-Lbc-mediated RhoA activation.

α6β4 Integrin Directs Alveolar Epithelial Migration

“…Central to this effect is the ability of a 6 b 4 integrin to activate Rac1, a small GTPase important in lamellipodial formation and directional migration (6). These studies replicate previous findings demonstrating that a 6 b 4 integrin controls motility by regulating Rac1 signaling further solidifying these fundamental signaling pathways identified as important for epithelial cell migration (7,8).…”

MUC5AC interactions with integrin β4 enhances the migration of lung cancer cells through FAK signaling

“…21,22,28,29 Both integrins and MUC5AC share the von Willebrand factor domain, 30,31 which is required for dimerization or oligomerization. We hypothesized that the presence of von Willebrand factor domains in both integrins and MUC5AC may lead to their interaction with each other.…”

“…26,48 In addition, integrins also activate metastatic signaling by binding with various oncogenes and growth factors. 21,22,28 Both integrins and MUC5AC have a von Willebrand factor domain, which is responsible for dimerization or oligomerization. 30,31 This raises the possibility that von Willebrand factor domain of the two molecules may interact with each other in lung cancer cells.…”

Integrin α6β4 Promotes Autocrine Epidermal Growth Factor Receptor (EGFR) Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor (HGF)

“…The ability of integrin ␣6␤4 to promote the expression and secretion of factors such as autotaxin, S100A4, VEGF, AREG, and EREG suggests that autocrine secretion is a major function of integrin ␣6␤4-mediated migration and invasion. Downstream of these secreted factors, integrin ␣6␤4 is also well known for cooperating with various growth factor receptors, including EGFR, c-Met, and LPAR1 to amplify Rho family GTPase family members Rac (11,53) and Rho (8,54). These events in turn permit cell polarization and enhanced cell motility and invasion.…”