Integrin α5/β1 Mediates Fibronectin-dependent Epithelial Cell Proliferation through Epidermal Growth Factor Receptor Activation

Human integrin α5 was transfected into the integrin α5/β1–negative intestinal epithelial cell line Caco-2 to study EGF receptor (EGFR) and integrin α5/β1 signaling interactions involved in epithelial cell proliferation. On uncoated or fibronectin-coated plastic, the integrin α5 and control (vector only) transfectants grew at similar rates. In the presence of the EGFR antagonistic mAb 225, the integrin α5 transfectants and controls were significantly growth inhibited on plastic. However, when cultured on fibronectin, the integrin α5 transfectants were not growth inhibited by mAb 225. The reversal of mAb 225–mediated growth inhibition on fibronectin for the integrin α5 transfectants correlated with activation of the EGFR, activation of MAPK, and expression of proliferating cell nuclear antigen. EGFR kinase activity was necessary for both MAPK activation and integrin α5/β1–mediated cell proliferation. Although EGFR activation occurred when either the integrin α5–transfected or control cells were cultured on fibronectin, coprecipitation of the EGFR with SHC could be demonstrated only in the integrin α5–transfected cells. These results suggest that integrin α5/β1 mediates fibronectin-induced epithelial cell proliferation through activation of the EGFR.