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

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

Author information

1
Field of Genomics, Genetics, and Development, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
2
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
3
Field of Genomics, Genetics, and Development, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA. Electronic address: locasale@cornell.edu.

Abstract

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.

PMID:
25456139
PMCID:
PMC4317399
DOI:
10.1016/j.celrep.2014.10.026
[Indexed for MEDLINE]
Free PMC Article

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