期刊
ONCOGENE
卷 28, 期 27, 页码 2485-2491出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.112
关键词
NMR; isotopomer; stable isotope labeling; O-linked N-acetylglucosamine; glucose
资金
- NIH [R21 DK070297, P41 RR02301]
- Human Metabolome database
- MDL database
- Department of Energy's Office of Biological and Environmental Research at Pacific Northwest National Laboratory
- Development of the program tca-CALC [RO1CA106650-02]
- University of Texas Southwestern Medical Center [H47669-16]
- Department of Veterans Affairs Merit Review Award to CR Malloy [RR02584]
Cell proliferation requires the coordinated activity of cytosolic and mitochondrial metabolic pathways to provide ATP and building blocks for DNA, RNA and protein synthesis. Many metabolic pathway genes are targets of the c-myc oncogene and cell-cycle regulator. However, the contribution of c-Myc to the activation of cytosolic and mitochondrial metabolic networks during cell-cycle entry is unknown. Here, we report the metabolic fates of [U-C-13] glucose in serum-stimulated myc(-/-) and myc(+/+) fibroblasts by C-13 isotopomer NMR analysis. We demonstrate that endogenous c-myc increased C-13 labeling of ribose sugars, purines and amino acids, indicating partitioning of glucose carbons into C1/folate and pentose phosphate pathways, and increased tricarboxylic acid cycle turnover at the expense of anaplerotic flux. Myc expression also increased global O-linked N-acetylglucosamine protein modi. cation, and inhibition of hexosamine biosynthesis selectively reduced growth of Myc-expressing cells, suggesting its importance in Myc-induced proliferation. These data reveal a central organizing function for the Myc oncogene in the metabolism of cycling cells. The pervasive deregulation of this oncogene in human cancers may be explained by its function in directing metabolic networks required for cell proliferation. Oncogene ( 2009) 28, 2485-2491; doi: 10.1038/onc.2009.112; published online 18 May 2009
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