The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels
Type
ArticleAuthors
Tong, WinghangSourbier, Carole
Kovtunovych, Gennadiy
Jeong, Suhyoung
Vira, Manish A.
Ghosh, Manik Chandra
Romero, Vladimir Valera
Sougrat, Rachid

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 LabCore Labs
Date
2011-09-11Embargo End Date
2012-09-11Permanent link to this record
http://hdl.handle.net/10754/561857
Metadata
Show full item recordAbstract
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.2011.07.018Sponsors
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 BVJournal
Cancer CellPubMed ID
21907923PubMed Central ID
PMC3174047Additional Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174047http://europepmc.org/articles/pmc3174047?pdf=render
ae974a485f413a2113503eed53cd6c53
10.1016/j.ccr.2011.07.018
Scopus Count
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