Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth
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Oncogenic K-Ras.pdf
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Author(s)
Danna, L. S.
Balestrieri, C.
Alberghina, L.
Chiaradonna, F.
Gaglio, Daniela
Metallo, Christian M.
Da Costa Gameiro Guerreiro, Paulo
Hiller, Karsten
Stephanopoulos, Gregory
Date Issued
August 2011
Journal
Molecular Systems Biology
Publisher
Nature Publishing Group
Citation
Gaglio, D. et al. “Oncogenic K-Ras Decouples Glucose and Glutamine Metabolism to Support Cancer Cell Growth.” Molecular Systems Biology 7.1 (2011): 523–523. © 2011 EMBO and Macmillan Publishers Limited
Version
Final published version
Abstract
Oncogenes such as K‐ras mediate cellular and metabolic transformation during tumorigenesis. To analyze K‐Ras‐dependent metabolic alterations, we employed [superscript 13]C metabolic flux analysis (MFA), non‐targeted tracer fate detection (NTFD) of [superscript 15]N‐labeled glutamine, and transcriptomic profiling in mouse fibroblast and human carcinoma cell lines. Stable isotope‐labeled glucose and glutamine tracers and computational determination of intracellular fluxes indicated that cells expressing oncogenic K‐Ras exhibited enhanced glycolytic activity, decreased oxidative flux through the tricarboxylic acid (TCA) cycle, and increased utilization of glutamine for anabolic synthesis. Surprisingly, a non‐canonical labeling of TCA cycle‐associated metabolites was detected in both transformed cell lines. Transcriptional profiling detected elevated expression of several genes associated with glycolysis, glutamine metabolism, and nucleotide biosynthesis upon transformation with oncogenic K‐Ras. Chemical perturbation of enzymes along these pathways further supports the decoupling of glycolysis and TCA metabolism, with glutamine supplying increased carbon to drive the TCA cycle. These results provide evidence for a role of oncogenic K‐Ras in the metabolic reprogramming of cancer cells.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
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Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license
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DOI of Published Version
https://doi.org/10.1038/msb.2011.56
