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.
|Number of pages||14|
|State||Published - Feb 8 2012|
Bibliographical noteFunding Information:
We thank Dr. A. Lane, Dr. S. Arumugam, J. Tan, and R. Burra (University of Louisville, Louisville, KY) for help with metabolic profiling analysis and Dr. A. Lane for valuable comments on the manuscript; Drs. A. Goga and A. Balakrishnan (University of California, San Francisco, San Francisco, CA) for useful discussion of preliminary results; L. Urisman (University of California, San Francisco, San Francisco, CA) for assistance with animal husbandry; and members of the Bishop Laboratory for valuable discussions and comments. NMR analyses were supported in part by National Institutes of Health (NIH) Grant P20RR018733 from the National Center for Research Resources and National Science Foundation (NSF) EPSCoR grant EPS-0447479. Metabolite profiling analysis was supported by NSF EPSCoR grant EPS-0447479, National Cancer Institute (NCI) grants 1R01CA118434-01A2 and 3R01 CA118434-02S1; and University of Louisville CTSPGP award (T.W.M.F.). The work was also supported by UCSF/G.W. Hooper Research Foundation Endowment Funds and by NCI Grant R35 CA44338 (J.M.B.); by UCSF Hellen Diller Family Comprehensive Cancer Center Pilot Grant and the UCSF Department of Radiology and Biomedical Imaging Seed Grant 10-09 (X.C. and Y.S.); by the Johns Hopkins Brain Science Institute through the NeuroTranslational Program (T.T. and D.V.F.); by NIH Grant R21NS074151 (to T.T.); and by Ministerio de Ciencia y Tecnología SAF2010-17573 and Junta de Andalucía, Proyectos de Investigación de Excelencia, Convocatoria 2010, CVI-6656, Spain (J.M.M. and F.J.A.).
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology