Targeting mitochondrial glutaminase activity inhibits oncogenic transformation

Jian Bin Wang, Jon W. Erickson, Reina Fuji, Sekar Ramachandran, Ping Gao, Ramani Dinavahi, Kristin F. Wilson, Andre L.B. Ambrosio, Sandra M.G. Dias, Chi V. Dang, Richard A. Cerione

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)207-219
Number of pages13
JournalCancer cell
Volume18
Issue number3
DOIs
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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