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Metabolic supervision by PPIP5K, an inositol pyrophosphate kinase/phosphatase, controls proliferation of the HCT116 tumor cell line
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- Chunfang Gu
- Signal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709;
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- Juan Liu
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710;
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- Xiaojing Liu
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710;
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- Haibo Zhang
- Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892
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- Ji Luo
- Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892
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- Huanchen Wang
- Signal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709;
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- Jason W. Locasale
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710;
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- Stephen B. Shears
- Signal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709;
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Description
<jats:title>Significance</jats:title> <jats:p>Central carbon metabolism has the overlapping functions of converting substrate into biomass and the extraction and storage of chemical energy. These metabolic pathways are rewired by cancer cells to selectively support increased biomass demands. This reprogramming is a potential therapeutic target if a molecular-level understanding of the relevant control processes can be attained. Through genomic editing of an HCT116 colonic tumor cell line, we uncover metabolic supervision by a single pair of cell-signaling enzymes, the PPIP5Ks. Our global measurements of steady-state metabolite levels, plus isotope tracing analysis, show in detail how HCT116 cells recruit PPIP5Ks to select specific metabolic pathways to provide adequate precursor supply for biomass production. Crucially, in the absence of PPIP5K activity, HCT116 tumorigenesis is reduced.</jats:p>
Journal
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 118 (10), 2021-03
Proceedings of the National Academy of Sciences
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Details 詳細情報について
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- CRID
- 1360861710252428416
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- ISSN
- 10916490
- 00278424
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- Data Source
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- Crossref