Regulation of tumor angiogenesis by EZH2

Chunhua Lu, 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. JenningsBlake 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)185-197
Number of pages13
JournalCancer cell
Volume18
Issue number2
DOIs
StatePublished - Aug 2010

Keywords

  • Cellcycle

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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