| Literature DB >> 20708159 |
Chunhua Lu1, Hee Dong Han, Lingegowda S Mangala, Rouba Ali-Fehmi, Christopher S Newton, Laurent Ozbun, Guillermo N Armaiz-Pena, Wei Hu, Rebecca L Stone, Adnan Munkarah, Murali K Ravoori, Mian M K Shahzad, Jeong-Won Lee, Edna Mora, Robert R Langley, Amy R Carroll, Koji Matsuo, Whitney A Spannuth, Rosemarie Schmandt, Nicholas B Jennings, Blake W Goodman, Robert B Jaffe, Alpa M Nick, Hye Sun Kim, Eylem Ozturk Guven, Ya-Huey Chen, Long-Yuan Li, Ming-Chuan Hsu, Robert L Coleman, George A Calin, Emir B Denkbas, Jae Yun Lim, Ju-Seog Lee, Vikas Kundra, Michael J Birrer, Mien-Chie Hung, Gabriel Lopez-Berestein, Anil K Sood.
Abstract
Although VEGF-targeted therapies are showing promise, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homolog 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome. The increase in endothelial EZH2 is a direct result of VEGF stimulation by a paracrine circuit that promotes angiogenesis by methylating and silencing vasohibin1 (vash1). Ezh2 silencing in the tumor-associated endothelial cells inhibited angiogenesis mediated by reactivation of VASH1, and reduced ovarian cancer growth, which is further enhanced in combination with ezh2 silencing in tumor cells. Collectively, these data support the potential for targeting ezh2 as an important therapeutic approach. 2010 Elsevier Inc. All rights reserved.Entities:
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Year: 2010 PMID： 20708159 PMCID： PMC2923653 DOI： 10.1016/j.ccr.2010.06.016
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743