Characterization of the usage of the serine metabolic network in human cancer

Cell Rep. 2014 Nov 20;9(4):1507-19. doi: 10.1016/j.celrep.2014.10.026. Epub 2014 Nov 6.


The serine, glycine, one-carbon (SGOC) metabolic network is implicated in cancer pathogenesis, but its general functions are unknown. We carried out a computational reconstruction of the SGOC network and then characterized its expression across thousands of cancer tissues. Pathways including methylation and redox metabolism exhibited heterogeneous expression indicating a strong context dependency of their usage in tumors. From an analysis of coexpression, simultaneous up- or downregulation of nucleotide synthesis, NADPH, and glutathione synthesis was found to be a common occurrence in all cancers. Finally, we developed a method to trace the metabolic fate of serine using stable isotopes, high-resolution mass spectrometry, and a mathematical model. Although the expression of single genes didn't appear indicative of flux, the collective expression of several genes in a given pathway allowed for successful flux prediction. Altogether, these findings identify expansive and heterogeneous functions for the SGOC metabolic network in human cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glutathione / biosynthesis
  • Glycine / metabolism
  • Humans
  • Metabolic Flux Analysis
  • Metabolic Networks and Pathways* / genetics
  • Models, Biological
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Nucleotides / biosynthesis
  • Purines / biosynthesis
  • Pyrimidines / biosynthesis
  • Serine / metabolism*


  • Nucleotides
  • Purines
  • Pyrimidines
  • Serine
  • Carbon
  • Glutathione
  • Glycine