{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:47:38Z","timestamp":1787017658445,"version":"build-2736575974"},"reference-count":53,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:p>\n                    c-Src is a non-receptor tyrosine kinase whose activity is induced by phosphorylation at Y418 and translocation from the cytoplasm to the cell membrane. Increased activity of c-Src has been associated with cell proliferation, matrix adhesion, motility, and apoptosis in tumors. Immunohistochemistry suggested that activated (pY\n                    <jats:sup>418<\/jats:sup>\n                    )-Src activity is increased in cyst-lining autosomal dominant polycystic kidney disease (ADPKD) epithelial cells in human and mouse ADPKD. Western blot analysis showed that SKI-606 (Wyeth) is a specific inhibitor of pY\n                    <jats:sup>418<\/jats:sup>\n                    -Src without demonstrable effects on epidermal growth factor receptor or ErbB2 activity in renal epithelia. In vitro studies on mouse inner medullary collecting duct (mIMCD) cells and human ADPKD cyst-lining epithelial cells showed that SKI-606 inhibited epithelial cell proliferation over a 24-h time frame. In addition, SKI-606 treatment caused a striking statistically significant decrease in adhesion of mIMCD and human ADPKD to extracellular collagen matrix. Retained viability of unattached cells was consistent with a primary effect on epithelial cell anchorage dependence mediated by the loss of extracellular matrix (ECM)-attachment due to \u03b1\n                    <jats:sub>2<\/jats:sub>\n                    \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    -integrin function. SKI-606-mediated attenuation of the human ADPKD hyperproliferative and hyper-ECM-adhesive epithelial cell phenotype in vitro was paralleled by retardation of the renal cystic phenotype of Pkd1 orthologous ADPKD heterozygous mice in vivo. This suggests that SKI-606 has dual effects on cystic epithelial cell proliferation and ECM adhesion and may have therapeutic potential for ADPKD patients.\n                  <\/jats:p>","DOI":"10.1152\/ajpcell.00163.2010","type":"journal-article","created":{"date-parts":[[2011,4,21]],"date-time":"2011-04-21T00:41:04Z","timestamp":1303346464000},"page":"C522-C529","source":"Crossref","is-referenced-by-count":55,"title":["c-Src inactivation reduces renal epithelial cell-matrix adhesion, proliferation, and cyst formation"],"prefix":"10.1152","volume":"301","author":[{"given":"Justine","family":"Elliott","sequence":"first","affiliation":[{"name":"Division of Nephrology, Mount Sinai School of Medicine, New York, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadezhda N.","family":"Zheleznova","sequence":"additional","affiliation":[{"name":"Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia D.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Mount Sinai School of Medicine, New York, New York; 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