title: Characterization of the usage of the serine metabolic network in human cancer.
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.
authors.affiliation: Field of Genomics, Genetics, and Development, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Mahya
authors.initials: M
authors.lastname: Mehrmohamadi
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Shestov
authors.affiliation: 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.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Locasale
mesh_terms: D002244:Carbon / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005978:Glutathione / Q000096:biosynthesis; D005998:Glycine / Q000378:metabolism; D006801:Humans; D064688:Metabolic Flux Analysis; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D009711:Nucleotides / Q000096:biosynthesis; D011687:Purines / Q000096:biosynthesis; D011743:Pyrimidines / Q000096:biosynthesis; D012694:Serine / Q000378:metabolism*
chemical_list: D009711:Nucleotides; D011687:Purines; D011743:Pyrimidines; D012694:Serine; D002244:Carbon; D005978:Glutathione; D005998:Glycine