Cell Metabolism
Volume 15, Issue 2, 8 February 2012, Pages 157-170
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Article
The Metabolic Profile of Tumors Depends on Both the Responsible Genetic Lesion and Tissue Type

https://doi.org/10.1016/j.cmet.2011.12.015Get rights and content
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Summary

The altered metabolism of tumors has been considered a target for anticancer therapy. However, the relationship between distinct tumor-initiating lesions and anomalies of tumor metabolism in vivo has not been addressed. We report that MYC-induced mouse liver tumors significantly increase both glucose and glutamine catabolism, whereas MET-induced liver tumors use glucose to produce glutamine. Increased glutamine catabolism in MYC-induced liver tumors is associated with decreased levels of glutamine synthetase (Glul) and the switch from Gls2 to Gls1 glutaminase. In contrast to liver tumors, MYC-induced lung tumors display increased expression of both Glul and Gls1 and accumulate glutamine. We also show that inhibition of Gls1 kills cells that overexpress MYC and catabolize glutamine. Our results suggest that the metabolic profiles of tumors are likely to depend on both the genotype and tissue of origin and have implications regarding the design of therapies targeting tumor metabolism.

Highlights

MYC and MET affect glucose and glutamine metabolism differently in the liver ► Tissue context affects the outcome of metabolic reprogramming by MYCMYC overexpression sensitizes cells to inhibition of Gls1 glutaminase

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