C-Myc activates multiple metabolic networks to generate substrates for cell-cycle entry

F. Morrish, N. Isern, M. Sadilek, M. Jeffrey, D. M. Hockenbery

Research output: Contribution to journalReview article

112 Scopus citations

Abstract

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- 13 C] glucose in serum-stimulated myc / and myc / fibroblasts by 13 C isotopomer NMR analysis. We demonstrate that endogenous c-myc increased 13 C 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 modification, 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.

Original languageEnglish (US)
Pages (from-to)2485-2491
Number of pages7
JournalOncogene
Volume28
Issue number27
DOIs
StatePublished - Jul 9 2009

Keywords

  • Glucose
  • Isotopomer
  • NMR
  • O-linked N-acetylglucosamine
  • Stable isotope labeling

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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