[PDF][PDF] Regulation of tumor angiogenesis by EZH2

C Lu, HD Han, LS Mangala, R Ali-Fehmi, CS Newton… - Cancer cell, 2010 - cell.com
C Lu, HD Han, LS Mangala, R Ali-Fehmi, CS Newton, L Ozbun, GN Armaiz-Pena, W Hu…
Cancer cell, 2010cell.com
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 …
Summary
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.
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