Targeting Mitochondrial Glutaminase Activity Inhibits Oncogenic Transformation

被引：692

作者：

Wang, Jian-Bin ^{[1
]}

Erickson, Jon W. ^{[1
,2
]}

Fuji, Reina ^{[1
]}

Ramachandran, Sekar ^{[1
,2
]}

Gao, Ping ^{[3
]}

Dinavahi, Ramani ^{[3
]}

Wilson, Kristin F. ^{[1
]}

Ambrosio, Andre L. B. ^{[1
]}

Dias, Sandra M. G. ^{[1
]}

Dang, Chi V. ^{[3
]}

Cerione, Richard A. ^{[1
,2
]}

机构：

[1] Cornell Univ, Dept Mol Med, Ithaca, NY 14853 USA

[2] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA

[3] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

来源：

CANCER CELL | 2010年 / 18卷 / 03期

基金：

美国国家卫生研究院;

关键词：

NF-KAPPA-B; BREAST-CANCER CELLS; RHO-GTPASES; CELLULAR-TRANSFORMATION; PYRUVATE-KINASE; TUMOR-GROWTH; METABOLISM; EXPRESSION; PROTEIN; CDC42;

D O I：

10.1016/j.ccr.2010.08.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Rho GTPases impact a number of activities important for oncogenesis. We describe a small molecule inhibitor that blocks oncogenic transformation induced by various Rho GTPases in fibroblasts, and the growth of human breast cancer and B lymphoma cells, without affecting normal cells. We identify the target of this inhibitor to be the metabolic enzyme glutaminase, which catalyzes the hydrolysis of glutamine to glutamate. We show that transformed fibroblasts and breast cancer cells exhibit elevated glutaminase activity that is dependent on Rho GTPases and NF-kappa B activity, and is blocked by the small molecule inhibitor. These findings highlight a previously unappreciated connection between Rho GTPase activation and cellular metabolism and demonstrate that targeting glutaminase activity can inhibit oncogenic transformation.

引用

页码：207 / 219

页数：13

共 38 条

[1] The cool-2/α-Pix protein mediates a Cdc42-Rac signaling cascade [J].