Disruption of fibronectin binding to the alpha 5 beta 1 integrin stimulates the expression of cyclin-dependent kinases and DNA synthesis through activation of extracellular signal-regulated kinase.

The Journal of Biological Chemistry
J GongM G Brattain

Abstract

The alpha 5 alpha 1 integrin, a fibronectin receptor, has been implicated in the control of cell growth and the regulation of gene expression. We report that disruption of ligation between alpha 5 alpha 1 and fibronectin by integrin alpha 5 subunit or fibronectin monoclonal antibodies stimulated DNA synthesis in growth-arrested FET human colon carcinoma cells. This stimulation only occurred when monoclonal antibody was added in the early G1 phase of the cell cycle after release from quiescence by fresh medium. Stimulation of DNA synthesis by alpha 5 or fibronectin antibody was concentration- and time-dependent. FET cells expressed alpha 4 beta 1 integrin (another fibronectin receptor); however, addition of anti-human integrin alpha 4 monoclonal antibody had no effect on DNA synthesis. Treatment with alpha 5 monoclonal antibody led to a marked increase in the expression of CDK4 in G1 phase of the cell cycle and consequently increased the phosphorylation of retinoblastoma protein. alpha 5 monoclonal antibody treatment increased both cyclin A- and cyclin E-associated kinase activity which was accompanied by increased protein levels of CDK2 and cyclin A. Western blotting of immunoprecipitates demonstrated increased CDK2-cyclin E an...Continue Reading

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Citations

Aug 21, 2009·Nature Reviews. Cancer·Mark B MeadsWilliam S Dalton
May 10, 2012·Cell Adhesion & Migration·Edna Cukierman, Daniel E Bassi
Sep 28, 2014·Rheumatology International·Jian TianGuang-Hua Lei
Sep 14, 2018·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Carmen Mariana Aanei, Lydia Campos Catafal
Mar 11, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jianhu ZhangMarc D Basson
Apr 23, 1999·The Journal of Biological Chemistry·D WangM G Brattain
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Feb 21, 2002·Journal of Vascular Surgery·Peter J ArmstrongJames R Elmore
Apr 25, 2006·Cancer Letters·Gertraud Orend, Ruth Chiquet-Ehrismann

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