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Pharmacological restoration of juxtacrine\u2010mediated death receptor signaling could prevent cancer cells from implanting in normal tissues such as the peritoneum. The results showed that BAY 11\u20107085 significantly inhibited peritoneal carcinomatosis in mice following the introduction of colon and pancreatic cancer cell lines into the intra\u2010abdominal cavity. Treatment with BAY 11\u20107085 restored juxtacrine death receptor signaling during the adhesion of the cancer cells to mesothelial cells, which line the peritoneum. BAY 11\u20107085 rapidly inhibited c\u2010FLIP<jats:sub>L<\/jats:sub> expression in colon and pancreatic cancer cell lines during adhesion to mesothelial cells. Pancreatic cancer cells sorted for high c\u2010FLIP<jats:sub>L<\/jats:sub> expression formed peritoneal implants much more readily than cells with low c\u2010FLIP<jats:sub>L<\/jats:sub> expression, and RNAi inhibition of c\u2010FLIP<jats:sub>L<\/jats:sub> in colon cancer cells dramatically reduced peritoneal implantation. This is a novel demonstration that the restoration of death receptor\u2010mediated apoptotic signaling in cancer cells through the pharmacological inhibition of c\u2010FLIP<jats:sub>L<\/jats:sub> can inhibit tumor implantation in a clinically relevant model of peritoneal carcinomatosis, a fatal disease. Pharmacological inhibitors of FLIP hold promise as a way to curtail cancer cell colonization of secondary tissues.<\/jats:p>","DOI":"10.1002\/ijc.26119","type":"journal-article","created":{"date-parts":[[2011,4,7]],"date-time":"2011-04-07T17:49:56Z","timestamp":1302198596000},"page":"1494-1503","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacologic downregulation of c\u2010FLIP<sub>L<\/sub> restores juxtacrine death receptor\u2010mediated apoptosis in cancer cells in a peritoneal carcinomatosis model"],"prefix":"10.1002","volume":"130","author":[{"given":"Yi","family":"Shen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Herde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brett 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