Journal
TRENDS IN MOLECULAR MEDICINE
Volume 19, Issue 2, Pages 74-82Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.molmed.2012.10.011
Keywords
rho; GTPase; signaling; glutamine; glutaminase; metabolism; cancer; Warburg
Funding
- NIGMS NIH HHS [R01 GM047458, R01 GM040654] Funding Source: Medline
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Recently, the small molecule 968 was found to block the Rho GTPase-dependent growth of cancer cells in cell culture and mouse xenografts, and when the target of 968 was found to be the mitochondrial enzyme glutaminase (GLS1), it revealed a surprising link between Rho GTPases and mitochondrial glutamine metabolism. Signal transduction via the Rho GTPases, together with NF-kappa B, appears to elevate mitochondrial glutaminase activity in cancer cells, thereby helping cancer cells satisfy their altered metabolic demands. Here, we review what is known about the mechanism of glutaminase activation in cancer cells, compare the properties of two distinct glutaminase inhibitors, and discuss recent findings that shed new light on how glutamine metabolism might affect cancer progression.
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