SIRT3 Opposes Reprogramming of Cancer Cell Metabolism through HIF1α Destabilization

Lydia W. S. Finley; Arkaitz Carracedo; Jaewon Lee; Amanda Souza; Ainara Egia; Jiangwen Zhang; Julie Teruya-Feldstein; Paula I. Moreira; Sandra M. Cardoso; Clary B. Clish; Pier Paolo Pandolfi; Marcia C. Haigis

doi:10.1016/j.ccr.2011.02.014

Back

SIRT3 Opposes Reprogramming of Cancer Cell Metabolism through HIF1α Destabilization

Journal article

Peer reviewed

SIRT3 Opposes Reprogramming of Cancer Cell Metabolism through HIF1α Destabilization

Lydia W. S. Finley, Arkaitz Carracedo, Jaewon Lee, Amanda Souza, Ainara Egia, Jiangwen Zhang, Julie Teruya-Feldstein, Paula I. Moreira, Sandra M. Cardoso, Clary B. Clish, …

Cancer cell, Vol.19(3), pp.416-428

03/08/2011

DOI: 10.1016/j.ccr.2011.02.014

PMID: 21397863

Files and links (1)

url

https://doi.org/10.1016/j.ccr.2011.02.014View

Published (Version of record) Open Access

Abstract

Tumor cells exhibit aberrant metabolism characterized by high glycolysis even in the presence of oxygen. This metabolic reprogramming, known as the Warburg effect, provides tumor cells with the substrates required for biomass generation. Here, we show that the mitochondria! NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect. Mechanistically, SIRT3 mediates metabolic reprogramming by destabilizing hypoxia-inducible factor-1 alpha (HIF1 alpha), a transcription factor that controls glycolytic gene expression. SIRT3 loss increases reactive oxygen species production, leading to HIF1 alpha stabilization. SIRT3 expression is reduced in human breast cancers, and its loss correlates with the upregulation of HIF1 alpha target genes. Finally, we find that SIRT3 overexpression represses glycolysis and proliferation in breast cancer cells, providing a metabolic mechanism for tumor suppression.

Cell Biology

Life Sciences & Biomedicine

Oncology

Science & Technology

Details

Title: Subtitle: SIRT3 Opposes Reprogramming of Cancer Cell Metabolism through HIF1α Destabilization
Creators: Lydia W. S. Finley - Harvard University
Arkaitz Carracedo - Beth Israel Deaconess Medical Center
Jaewon Lee - Harvard University
Amanda Souza - Broad Institute
Ainara Egia - Beth Israel Deaconess Medical Center
Jiangwen Zhang - Harvard University
Julie Teruya-Feldstein - Memorial Sloan Kettering Cancer Center
Paula I. Moreira - Centro de Neurociências e Biologia Celular
Sandra M. Cardoso - Centro de Neurociências e Biologia Celular
Clary B. Clish - Broad Institute
Pier Paolo Pandolfi - Beth Israel Deaconess Medical Center
Marcia C. Haigis - Harvard University
Resource Type: Journal article
Publication Details: Cancer cell, Vol.19(3), pp.416-428
DOI: 10.1016/j.ccr.2011.02.014
PMID: 21397863
ISSN: 1535-6108
eISSN: 1878-3686
Publisher: Elsevier
Number of pages: 13
Grant note: Ramon y Cajal award; Spanish Government Paul F. Glenn Foundation Muscular Dystrophy Association National Science Foundation; National Science Foundation (NSF) Alexander and Margaret Stewart Trust AG032375 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Language: English
Date published: 03/08/2011
Academic Unit: Surgery
Record Identifier: 9985240990202771

Metrics

1 Record Views

699 Times Cited - Web of Science