| Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance. | |
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MedLine Citation:
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PMID: 18718909 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The switch of cellular metabolism from mitochondrial respiration to glycolysis is the hallmark of cancer cells and associated with tumor malignancy. However, the mechanism of this metabolic switch remains largely unknown. Herein, we reported that hypoxia-inducible factor-1 (HIF-1) induced pyruvate dehydrogenase kinase-3 (PDK3) expression leading to inhibition of mitochondrial respiration. Promoter activity assay, small interference RNA knockdown assay, and chromatin immunoprecipitation assay demonstrated that hypoxia-induced PDK3 gene activity was regulated by HIF-1 at the transcriptional level. Forced expression of PDK3 in cancer cells resulted in increased lactic acid accumulation and drugs resistance, whereas knocking down PDK3 inhibited hypoxia-induced cytoplasmic glycolysis and cell survival. These data demonstrated that increased PDK3 expression due to elevated HIF-1alpha in cancer cells may play critical roles in metabolic switch during cancer progression and chemoresistance in cancer therapy. |
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Authors:
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Chun-Wun Lu; Shih-Chieh Lin; Ko-Fan Chen; Yen-Yu Lai; Shaw-Jenq Tsai |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-08-21 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 283 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-10-13 Completed Date: 2008-11-25 Revised Date: 2013-06-05 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 28106-14 Citation Subset: IM |
Affiliation:
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Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 701, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Differentiation Cell Hypoxia Cell Line, Tumor Cell Survival Chromatin Immunoprecipitation Drug Resistance* Drug Resistance, Neoplasm* Gene Expression Regulation* Gene Expression Regulation, Neoplastic* HeLa Cells Humans Hypoxia-Inducible Factor 1 / genetics* Models, Biological Protein-Serine-Threonine Kinases / biosynthesis* RNA, Small Interfering / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Hypoxia-Inducible Factor 1; 0/RNA, Small Interfering; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.2/pyruvate dehydrogenase (acetyl-transferring) kinase |
| Comments/Corrections | |
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