TY - JOUR
T1 - The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels
AU - Tong, Winghang
AU - Sourbier, Carole
AU - Kovtunovych, Gennadiy
AU - Jeong, Suhyoung
AU - Vira, Manish A.
AU - Ghosh, Manik Chandra
AU - Romero, Vladimir Valera
AU - Sougrat, Rachid
AU - Vaulont, Sophie
AU - Viollet, Benoît
AU - Kim, Yeongsang
AU - Lee, Sunmin
AU - Trepel, Jane B.
AU - Srinivasan, Ramaprasad
AU - Bratslavsky, Gennady
AU - Yang, Youfeng
AU - Linehan, William Marston
AU - Rouault, Tracey A.
N1 - KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: 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.
PY - 2011/9/11
Y1 - 2011/9/11
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/561857
UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174047
UR - http://www.scopus.com/inward/record.url?scp=80052572942&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2011.07.018
DO - 10.1016/j.ccr.2011.07.018
M3 - Article
C2 - 21907923
SN - 1535-6108
VL - 20
SP - 315
EP - 327
JO - Cancer Cell
JF - Cancer Cell
IS - 3
ER -
