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    The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels

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    nihms316774.pdf
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    Accepted manuscript
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    Type
    Article
    Authors
    Tong, Winghang
    Sourbier, Carole
    Kovtunovych, Gennadiy
    Jeong, Suhyoung
    Vira, Manish A.
    Ghosh, Manik Chandra
    Romero, Vladimir Valera
    Sougrat, Rachid cc
    Vaulont, Sophie
    Viollet, Benoît
    Kim, Yeongsang
    Lee, Sunmin
    Trepel, Jane B.
    Srinivasan, Ramaprasad
    Bratslavsky, Gennady
    Yang, Youfeng
    Linehan, William Marston
    Rouault, Tracey A.
    KAUST Department
    Imaging and Characterization Core Lab
    Core Labs
    Date
    2011-09-11
    Embargo End Date
    2012-09-11
    Permanent link to this record
    http://hdl.handle.net/10754/561857
    
    Metadata
    Show full item record
    Abstract
    Inactivation of the TCA cycle enzyme, fumarate hydratase (FH), drives a metabolic shift to aerobic glycolysis in FH-deficient kidney tumors and cell lines from patients with hereditary leiomyomatosis renal cell cancer (HLRCC), resulting in decreased levels of AMP-activated kinase (AMPK) and p53 tumor suppressor, and activation of the anabolic factors, acetyl-CoA carboxylase and ribosomal protein S6. Reduced AMPK levels lead to diminished expression of the DMT1 iron transporter, and the resulting cytosolic iron deficiency activates the iron regulatory proteins, IRP1 and IRP2, and increases expression of the hypoxia inducible factor HIF-1α, but not HIF-2α. Silencing of HIF-1α or activation of AMPK diminishes invasive activities, indicating that alterations of HIF-1α and AMPK contribute to the oncogenic growth of FH-deficient cells. © 2011 Elsevier Inc.
    Citation
    Tong, W.-H., Sourbier, C., Kovtunovych, G., Jeong, S. Y., Vira, M., Ghosh, M., … Rouault, T. A. (2011). The Glycolytic Shift in Fumarate-Hydratase-Deficient Kidney Cancer Lowers AMPK Levels, Increases Anabolic Propensities and Lowers Cellular Iron Levels. Cancer Cell, 20(3), 315–327. doi:10.1016/j.ccr.2011.07.018
    Sponsors
    The authors thank our colleagues and thank the intramural programs of the National Institute of Child Health and Human Development and the National Cancer Institute for support.
    Publisher
    Elsevier BV
    Journal
    Cancer Cell
    DOI
    10.1016/j.ccr.2011.07.018
    PubMed ID
    21907923
    PubMed Central ID
    PMC3174047
    Additional Links
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174047
    http://europepmc.org/articles/pmc3174047?pdf=render
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ccr.2011.07.018
    Scopus Count
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    Articles; Imaging and Characterization Core Lab

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