Heterogeneity of tumor-induced gene expression changes in the human metabolic network
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Vander Heiden_Heterogeneity.pdf
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Author(s)
Hu, Jie
Locasale, Jason W.
Bielas, Jason H.
O'Sullivan, Jacintha
Sheahan, Kieran
Cantley, Lewis C.
Vander Heiden, Matthew G.
Vitkup, Dennis
Date Issued
April 2013
Journal
Nature Biotechnology
Publisher
Nature Publishing Group
Citation
Hu, J., et al. (2013). "Heterogeneity of tumor-induced gene expression changes in the human metabolic network." Nature Biotechnology 31(6): 522-529.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/nbt.2530
