Regulation of Tumor Angiogenesis by EZH2

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2010 Aug 17

PMID 20708159

Citations 227

Authors

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 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

Affiliations

Soon will be listed here.

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.

Citing Articles

Polycomb repressive complex 2 (PRC2) pathway's role in cancer cell plasticity and drug resistance.

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PMID: 40048009 DOI: 10.1007/s10142-025-01563-8.

Treating human cancer by targeting EZH2.

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Enhancer zeste homolog 2 (EZH2) targeting by small interfering RNA (siRNA); recent advances and prospect.

Hsu C, Mohammed A, Hjazi A, Uthirapathy S, Renuka J, Singh A Naunyn Schmiedebergs Arch Pharmacol. 2025; .

PMID: 39960560 DOI: 10.1007/s00210-025-03883-9.

EZH2 serves as a viable therapeutic target for myeloma-induced osteolytic bone destruction.

Liu R, Li Z, Chen R, Fang Z, Liu Z, Liu H Nat Commun. 2025; 16(1):1206.

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Assessment of the Therapeutic Potential of Enhancer of Zeste Homolog 2 Inhibition in a Murine Model of Bronchiolitis Obliterans Syndrome.

Matsudo K, Takamori S, Takenaka T, Shimokawa M, Hashinokuchi A, Nagano T Transpl Int. 2024; 37:13227.

PMID: 39524044 PMC: 11543400. DOI: 10.3389/ti.2024.13227.

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