Oncogenic K‐Ras decouples glucose and glutamine metabolism to support cancer cell growth

Molecular Systems Biology

Daniela Gaglio¹  Christian M Metallo²  Paulo A Gameiro²  Karsten Hiller²  Lara Sala Danna¹  Chiara Balestrieri¹  Lilia Alberghina¹  Gregory Stephanopoulos² 

[1] Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy;Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

关键词: cancer;    metabolic flux analysis;    metabolism;    Ras;    transcriptional analysis;   

DOI  :  10.1038/msb.2011.56

来源: Wiley

【 摘 要 】

Oncogenes such as K-ras mediate cellular and metabolic transformation during tumorigenesis. To analyze K-Ras-dependent metabolic alterations, we employed ¹³C metabolic flux analysis (MFA), non-targeted tracer fate detection (NTFD) of ¹⁵N-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 tra

【 授权许可】

CC BY-NC-SA   
Copyright © 2011 EMBO and Macmillan Publishers Limited

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