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Cancer Cell. 2010 Sep 14;18(3):207-19. doi: 10.1016/j.ccr.2010.08.009.

Targeting mitochondrial glutaminase activity inhibits oncogenic transformation.

Author information

1
Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA.

Erratum in

  • Cancer Cell. 2010 Oct 19;18(4):397.

Abstract

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-κB 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.

PMID:
20832749
PMCID:
PMC3078749
DOI:
10.1016/j.ccr.2010.08.009
[Indexed for MEDLINE]
Free PMC Article

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