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Cancer Res. 2012 Jul 15;72(14):3582-92. doi: 10.1158/0008-5472.CAN-11-2876. Epub 2012 May 16.

Cancer angiogenesis induced by Kaposi sarcoma-associated herpesvirus is mediated by EZH2.

Author information

  • 1Department of Medicine, The University of Minnesota, Minneapolis, Minnesota, USA. meilan.he@gmail.com

Erratum in

  • Cancer Res. 2013 Sep 1;73(17):5603-5.

Abstract

EZH2 is a component of the epigenetic regulator PRC2 that suppresses gene expression. Elevated expression of EZH2 is common in human cancers and is associated with tumor progression and poor prognosis. In this study, we show that EZH2 elevation is associated with epigenetic modifications of Kaposi sarcoma-associated herpesvirus (KSHV), an oncogenic virus that promotes the development of Kaposi sarcoma and other malignancies that occur in patients with chronic HIV infections. KSHV induction of EZH2 expression was essential for KSHV-induced angiogenesis. High expression of EZH2 was observed in Kaposi sarcoma tumors. In cell culture, latent KSHV infection upregulated the expression of EZH2 in human endothelial cells through the expression of vFLIP and LANA, two KSHV-latent genes that activate the NF-κB pathway. KSHV-mediated upregulation of EZH2 was required for the induction of Ephrin-B2, an essential proangiogenic factor that drives endothelial cell tubule formation. Taken together, our findings indicate that KSHV regulates the host epigenetic modifier EZH2 to promote angiogenesis.

PMID:
22593192
[PubMed - indexed for MEDLINE]
PMCID:
PMC4034471
Free PMC Article

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