title: Regulation of tumor angiogenesis by EZH2.
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.
authors: Department of Gynecologic Oncology, U.T. M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Chunhua
authors: C
authors: Lu
authors: Hee Dong
authors: HD
authors: Han
authors: Lingegowda S
authors: LS
authors: Mangala
authors: Rouba
authors: R
authors: Ali-Fehmi
authors: Christopher S
authors: CS
authors: Newton
authors: Laurent
authors: L
authors: Ozbun
authors: Guillermo N
authors: GN
authors: Armaiz-Pena
authors: Wei
authors: W
authors: Hu
authors: Rebecca L
authors: RL
authors: Stone
authors: Adnan
authors: A
authors: Munkarah
authors: Murali K
authors: MK
authors: Ravoori
authors: Mian M K
authors: MM
authors: Shahzad
authors: Jeong-Won
authors: JW
authors: Lee
authors: Edna
authors: E
authors: Mora
authors: Robert R
authors: RR
authors: Langley
authors: Amy R
authors: AR
authors: Carroll
authors: Koji
authors: K
authors: Matsuo
authors: Whitney A
authors: WA
authors: Spannuth
authors: Rosemarie
authors: R
authors: Schmandt
authors: Nicholas B
authors: NB
authors: Jennings
authors: Blake W
authors: BW
authors: Goodman
authors: Robert B
authors: RB
authors: Jaffe
authors: Alpa M
authors: AM
authors: Nick
authors: Hye Sun
authors: HS
authors: Kim
authors: Eylem Ozturk
authors: EO
authors: Guven
authors: Ya-Huey
authors: YH
authors: Chen
authors: Long-Yuan
authors: LY
authors: Li
authors: Ming-Chuan
authors: MC
authors: Hsu
authors: Robert L
authors: RL
authors: Coleman
authors: George A
authors: GA
authors: Calin
authors: Emir B
authors: EB
authors: Denkbas
authors: Jae Yun
authors: JY
authors: Lim
authors: Ju-Seog
authors: JS
authors: Lee
authors: Vikas
authors: V
authors: Kundra
authors: Michael J
authors: MJ
authors: Birrer
authors: Mien-Chie
authors: MC
authors: Hung
authors: Gabriel
authors: G
authors: Lopez-Berestein
authors: Anil K
authors: AK
authors: Sood
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D017931:DNA Primers; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D020868:Gene Silencing; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000473:pathology; D063151:Polycomb Repressive Complex 2
chemical_list: D017931:DNA Primers; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2