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We previously reported that kidney epithelial cell\u2010derived Madin\u2010Darby Canine Kidney cells were transformed into mesenchymal\u2010like cells by gene transfection of CRT. In this study, we investigated the altered characteristics of cell adhesion in these epithelial\u2010mesenchymal transition (EMT)\u2010like cells. Several extracellular matrix substrata were tested, and cell adhesion to fibronectin was found to be specifically increased in the CRT\u2010overexpressing cells compared to controls. The expression of integrins was significantly up\u2010regulated in subunits \u03b15 and \u03b1V, resulting in an increase in the formation of complexes such as \u03b15\u03b21 and \u03b1V\u03b23. These integrins also contributed to the enhanced binding of fibronectin. In the CRT\u2010overexpressing cells, the phosphorylation of Akt, a downstream target of integrin\u2010linked kinase (ILK), was up\u2010regulated on attachment to fibronectin or collagen IV. Integrin\u2010associated signaling through ILK was also promoted on attachment to fibronectin, suggesting some of the correlation between ILK and Akt in the CRT\u2010overexpressing cells. Furthermore, on treatment with 1,2\u2010bis (2\u2010aminophenoxy) ethane\u2010N,N,N',N'\u2010tetraacetic acid tetra (acetoxymethyl) ester, a membrane\u2010permeable Ca\n                    <jats:sup>2+<\/jats:sup>\n                    chelator, the enhanced Akt signaling was suppressed with a concomitant decrease in the formation of complexes between integrins and ILK in the CRT\u2010overexpressing cells. In conclusion, these findings demonstrate that CRT regulates cell\u2010substratum adhesion by modulating integrin\u2010associated signaling through altered Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis in the CRT\u2010overexpressing EMT\u2010like cells, suggesting a novel regulatory role for CRT in EMT. J. Cell. Biochem. 112: 2518\u20132528, 2011. \u00a9 2011 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/jcb.23176","type":"journal-article","created":{"date-parts":[[2011,5,6]],"date-time":"2011-05-06T09:25:31Z","timestamp":1304673931000},"page":"2518-2528","source":"Crossref","is-referenced-by-count":30,"title":["Alteration of integrin\u2010dependent adhesion and signaling in EMT\u2010like MDCK cells established through overexpression of 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