Targeting HSF1 sensitizes cancer cells to HSP90 inhibition

摘要: // Yaoyu Chen 1,* , Jinyun Alice Loo 1 Savina Jaeger Linda Bagdasarian 2 Jianjun Yu 3 Franklin Chung Joshua Korn David Ruddy Ribo Guo Margaret E. Mclaughlin Fei Feng Ping Zhu Frank Stegmeier Raymond Pagliarini Dale Porter and Wenlai Zhou Oncology, Novartis Institutes for Biomedical Research, Cambridge, MA, USA Oncology Translational Emeryville, CA, * These authors contributed equally to this work. Correspondence: Zhou, email: Keywords : HSF1, cancer cells, HSP90 inhibitor, Melanoma, HCC, DEDD2. Received April 19, 2013 Accepted 21, Published 23, Abstract The molecular chaperone heat shock protein 90 (HSP90) facilitates the appropriate folding of various oncogenic proteins is necessary survival some cells. therefore an attractive drug target, but efficacy inhibitor may be limited by inhibition induced feedback mechanisms. Through pooled RNA interference screens, we identified that factor 1( HSF1 ) a sensitizer inhibitor. A striking combinational effect was observed when knockdown plus with inhibitors treatment in cell lines tumor mouse models. Interestingly, highly expressed hepatocellular carcinoma (HCC) patient samples HCC sensitive treatment, indicating potential indication treatment. To understand mechanism effect, -target gene DEDD2 involved attenuating inhibitors. Thus, transcriptional activities provide limiting inhibitor’s activity, targeting new avenue enhance activity human cancers.