Integrin alpha 5/beta 1 mediates fibronectin-dependent epithelial cell proliferation through epidermal growth factor receptor activation

摘要

Human integrin alpha 5 was transfected into the integrin alpha 5/beta 1-negative intestinal epithelial cell line Caco-2 to study EGF receptor (EGFR) and integrin alpha 5/beta 1 signaling interactions involved in epithelial cell proliferation. On uncoated or fibronectin-coated plastic, the integrin alpha 5 and control (vector only) transfectants grew at similar rates. In the presence of the EGFR antagonistic mAb 225, the integrin alpha 5 transfectants and controls were significantly growth inhibited on plastic. However, when cultured on fibronectin, the integrin alpha 5 transfectants were not growth inhibited by mAb 225. The reversal of mAb 225-mediated growth inhibition on fibronectin for the integrin alpha 5 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 alpha 5/beta 1-mediated cell proliferation. Although EGFR activation occurred when either the integrin alpha 5-transfected or control cells were cultured on fibronectin, coprecipitation of the EGFR with SHC could be demonstrated only in the integrin alpha 5-transfected cells. These results suggest that integrin alpha 5/beta 1 mediates fibronectin-induced epithelial cell proliferation through activation of the EGFR. [References: 80]