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Remarkably, p21 was found to bind to CDK8 and stimulate its kinase activity. p21 and CDK8 also cooperate in the formation of internucleolar bodies, where both proteins accumulate. A CDK8 inhibitor suppresses damage-induced tumor-promoting paracrine activities of tumor cells and normal fibroblasts and reverses the increase in tumor engraftment and serum mitogenic activity in mice pretreated with a chemotherapeutic drug. The inhibitor also increases the efficacy of chemotherapy against xenografts formed by tumor cell\/fibroblast mixtures. Microarray data analysis revealed striking correlations between CDK8 expression and poor survival in breast and ovarian cancers. CDK8 inhibition offers a promising approach to increasing the efficacy of cancer chemotherapy.<\/jats:p>","DOI":"10.1073\/pnas.1206906109","type":"journal-article","created":{"date-parts":[[2012,8,6]],"date-time":"2012-08-06T22:50:06Z","timestamp":1344293406000},"page":"13799-13804","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":173,"title":["Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities"],"prefix":"10.1073","volume":"109","author":[{"given":"Donald C.","family":"Porter","sequence":"first","affiliation":[{"name":"Senex Biotechnology, Inc., Columbia, SC 29208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Farmaki","sequence":"additional","affiliation":[{"name":"Laboratory of Biological Chemistry, University of Athens Medical School, 115 27 Athens, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Altilia","sequence":"additional","affiliation":[{"name":"Senex Biotechnology, Inc., Columbia, SC 29208;"},{"name":"Cancer Center, Ordway Research Institute, Albany, NY 12208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary P.","family":"Schools","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208;"},{"name":"Cancer Center, Ordway Research Institute, Albany, NY 12208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah K.","family":"West","sequence":"additional","affiliation":[{"name":"Senex Biotechnology, Inc., Columbia, SC 29208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bey-Dih","family":"Chang","sequence":"additional","affiliation":[{"name":"Senex Biotechnology, Inc., Columbia, SC 29208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoliy T.","family":"Puzyrev","sequence":"additional","affiliation":[{"name":"Senex Biotechnology, Inc., Columbia, SC 29208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-uk","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208;"},{"name":"Cancer Center, Ordway Research Institute, Albany, NY 12208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Rokow-Kittell","sequence":"additional","affiliation":[{"name":"Senex Biotechnology, Inc., Columbia, SC 29208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence T.","family":"Friedhoff","sequence":"additional","affiliation":[{"name":"Senex Biotechnology, Inc., Columbia, SC 29208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios G.","family":"Papavassiliou","sequence":"additional","affiliation":[{"name":"Laboratory of Biological Chemistry, University of Athens Medical School, 115 27 Athens, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swathi","family":"Kalurupalle","sequence":"additional","affiliation":[{"name":"Cancer Center, Ordway Research Institute, Albany, NY 12208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Hurteau","sequence":"additional","affiliation":[{"name":"Cancer Center, Ordway Research Institute, Albany, NY 12208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil S.","family":"Baran","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balazs","family":"Gyorffy","sequence":"additional","affiliation":[{"name":"Research Laboratory for Pediatrics and Nephrology, Hungarian Academy of Sciences, Budapest H-1083, Hungary; 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