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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Mehrmohamadi, M; Liu, X; Shestov, AA; Locasale, JW

Published Date

  • November 20, 2014

Published In

Volume / Issue

  • 9 / 4

Start / End Page

  • 1507 - 1519

PubMed ID

  • 25456139

Pubmed Central ID

  • 25456139

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2014.10.026

Language

  • eng

Conference Location

  • United States