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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels
Cancer Cell, Volume 20, No. 3, Year 2011
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Description
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.
Authors & Co-Authors
Tong, Wing Hang
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Sourbier, Carole
United States, Rockville
National Cancer Institute Nci
Kovtunovych, Gennady
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Jeong, Suh Young
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Vira, Manish
United States, New York
Albert Einstein College of Medicine of Yeshiva University
Ghosh, Manik
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Romero, Vladimir Valera
United States, Rockville
National Cancer Institute Nci
Sougrat, Rachid
Saudi Arabia, Thuwal
King Abdullah University of Science and Technology
Vaulont, Sophie
France, Paris
Institut Cochin
Viollet, Benoit
France, Paris
Institut Cochin
Kim, Yeong Sang
United States, Rockville
National Cancer Institute Nci
Lee, Sunmin
United States, Rockville
National Cancer Institute Nci
Trepel, Jane
United States, Rockville
National Cancer Institute Nci
Srinivasan, Ramaprasad
United States, Rockville
National Cancer Institute Nci
Bratslavsky, Gennady
United States, Rockville
National Cancer Institute Nci
Yang, Youfeng
United States, Rockville
National Cancer Institute Nci
Linehan, W. Marston
United States, Rockville
National Cancer Institute Nci
Rouault, Tracey Ann
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Statistics
Citations: 192
Authors: 18
Affiliations: 5
Identifiers
Doi:
10.1016/j.ccr.2011.07.018
ISSN:
15356108
e-ISSN:
18783686
Research Areas
Cancer
Noncommunicable Diseases