| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2042228 | Cell Reports | 2014 | 13 Pages |
•Reconstruction of the SGOC metabolic network was carried out in cancer and normal tissues•Most pathways show heterogeneity across and within tumor and normal tissue types•Serine flux simultaneously distributes to nucleotides, NAPDH, and redox metabolism•Flux analysis of serine shows that gene expression patterns can predict flux
SummaryThe 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.
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