Journal
CANCER CELL
Volume 18, Issue 3, Pages 207-219Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2010.08.009
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Funding
- National Institutes of Health
- Susan G. Komen Breast Cancer Foundation
- National Cancer Institute, National Institutes of Health
- Leukemia and Lymphoma Society
- AACR Stand-Up-to-Cancer Initiative
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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.
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