title: Heterogeneity of tumor-induced gene expression changes in the human metabolic network.
abstract: Reprogramming of cellular metabolism is an emerging hallmark of neoplastic transformation. However, it is not known how the expression of metabolic genes in tumors differs from that in normal tissues, or whether different tumor types exhibit similar metabolic changes. Here we compare expression patterns of metabolic genes across 22 diverse types of human tumors. Overall, the metabolic gene expression program in tumors is similar to that in the corresponding normal tissues. Although expression changes of some metabolic pathways (e.g., upregulation of nucleotide biosynthesis and glycolysis) are frequently observed across tumors, expression changes of other pathways (e.g., oxidative phosphorylation) are very heterogeneous. Our analysis also suggests that the expression changes of some metabolic genes (e.g., isocitrate dehydrogenase and fumarate hydratase) may enhance or mimic the effects of recurrent mutations in tumors. On the level of individual biochemical reactions, many hundreds of metabolic isoenzymes show significant and tumor-specific expression changes. These isoenzymes are potential targets for anticancer therapy.
authors.affiliation: Center for Computational Biology and Bioinformatics and Initiative in Systems Biology, Columbia University, New York, New York, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.forename: Jason W
authors.initials: JW
authors.lastname: Locasale
authors.forename: Jason H
authors.initials: JH
authors.lastname: Bielas
authors.forename: Jacintha
authors.initials: J
authors.lastname: O'Sullivan
authors.forename: Kieran
authors.initials: K
authors.lastname: Sheahan
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Cantley
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Vander Heiden
authors.forename: Dennis
authors.initials: D
authors.lastname: Vitkup
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation
chemical_list: D007527:Isoenzymes; D007521:Isocitrate Dehydrogenase