Integrin alpha5/beta1 mediates fibronectin-dependent epithelial cell proliferation through epidermal growth factor receptor activation.
Human integrin alpha5 was transfected into the integrin alpha5/beta1-negative intestinal epithelial cell line Caco-2 to study EGF receptor (EGFR) and integrin alpha5/beta1 signaling interactions involved in epithelial cell proliferation. On uncoated or fibronectin-coated plastic, the integrin alpha5 and control (vector only) transfectants grew at similar rates. In the presence of the EGFR antagonistic mAb 225, the integrin alpha5 transfectants and controls were significantly growth inhibited on plastic. However, when cultured on fibronectin, the integrin alpha5 transfectants were not growth inhibited by mAb 225. The reversal of mAb 225-mediated growth inhibition on fibronectin for the integrin alpha5 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 alpha5/beta1-mediated cell proliferation. Although EGFR activation occurred when either the integrin alpha5-transfected or control cells were cultured on fibronectin, coprecipitation of the EGFR with SHC could be demonstrated only in the integrin alpha5-transfected cells. These results suggest that integrin alpha5/beta1 mediates fibronectin-induced epithelial cell proliferation through activation of the EGFR.
Kuwada
S K
SK
Division of Gastroenterology, University of Utah and Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah 84132, USA. scott.kuwada@hsc.utah.edu
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D015703:Antigens, CD / Q000096:biosynthesis; D002455:Cell Division; D066246:ErbB Receptors / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039482:Integrin alpha5; D016023:Integrins / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D005353:Fibronectins; D039482:Integrin alpha5; D016023:Integrins; D017469:Receptors, Fibronectin; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases