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dc.contributor.authorTong, Winghang
dc.contributor.authorSourbier, Carole
dc.contributor.authorKovtunovych, Gennadiy
dc.contributor.authorJeong, Suhyoung
dc.contributor.authorVira, Manish A.
dc.contributor.authorGhosh, Manik Chandra
dc.contributor.authorRomero, Vladimir Valera
dc.contributor.authorSougrat, Rachid
dc.contributor.authorVaulont, Sophie
dc.contributor.authorViollet, Benoît
dc.contributor.authorKim, Yeongsang
dc.contributor.authorLee, Sunmin
dc.contributor.authorTrepel, Jane B.
dc.contributor.authorSrinivasan, Ramaprasad
dc.contributor.authorBratslavsky, Gennady
dc.contributor.authorYang, Youfeng
dc.contributor.authorLinehan, William Marston
dc.contributor.authorRouault, Tracey A.
dc.date.accessioned2015-08-03T09:32:37Z
dc.date.available2015-08-03T09:32:37Z
dc.date.issued2011-09-11
dc.identifier.citationTong, 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
dc.identifier.issn15356108
dc.identifier.pmid21907923
dc.identifier.doi10.1016/j.ccr.2011.07.018
dc.identifier.urihttp://hdl.handle.net/10754/561857
dc.description.abstractInactivation 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.
dc.description.sponsorshipThe 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.
dc.publisherElsevier BV
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174047
dc.relation.urlhttp://europepmc.org/articles/pmc3174047?pdf=render
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in [JournalTitle]. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in [JournalTitle], [[Volume], [Issue], (2011-09-11)] DOI: 10.1016/j.ccr.2011.07.018 . © 2011. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rightsThis file is an open access version redistributed from: http://europepmc.org/articles/pmc3174047?pdf=render
dc.titleThe glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels
dc.typeArticle
dc.contributor.departmentImaging and Characterization Core Lab
dc.contributor.departmentCore Labs
dc.identifier.journalCancer Cell
dc.identifier.pmcidPMC3174047
dc.rights.embargodate2012-09-11
dc.eprint.versionPost-print
dc.contributor.institutionMolecular Medicine Program, Eunice Kennedy Shriver National Institute of Child Health and Development, Bethesda, MD, United States
dc.contributor.institutionUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States
dc.contributor.institutionAlbert Einstein College of Medicine, New York, United States
dc.contributor.institutionInstitut Cochin, Université Paris Descartes, CNRS (UMR8104), Paris, France
dc.contributor.institutionInserm U 1016, Paris, France
dc.contributor.institutionMedical Oncology Branch, National Cancer Institute, Bethesda, MD, United States
kaust.personSougrat, Rachid
refterms.dateFOA2020-04-22T11:54:10Z


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