HIF-1-mediated suppression of acyl-CoA dehydrogenases and fatty acid oxidation is critical for cancer progression

De Huang, Tingting Li, Xinghua Li, Long Zhang, Linchong Sun, Xiaoping He, Xiuying Zhong, Dongya Jia, Libing Song, Gregg L Semenza, Ping Gao, Huafeng Zhang

Research output: Contribution to journalArticle

Abstract

Hypoxia-inducible factor 1 (HIF-1) mediates a metabolic switch that blocks the conversion of pyruvate to acetyl-CoA in cancer cells. Here, we report that HIF-1α also inhibits fatty acid β-oxidation (FAO), another major source of acetyl-CoA. We identified a PGC-1β-mediated pathway by which HIF-1 inhibits the medium- and long-chain acyl-CoA dehydrogenases (MCAD and LCAD), resulting in decreased reactive oxygen species levels and enhanced proliferation. Surprisingly, we further uncovered that blocking LCAD, but not MCAD, blunts PTEN expression and dramatically affects tumor growth invivo. Analysis of 158 liver cancer samples showed that decreased LCAD expression predicts patient mortality. Altogether, we have identified a previously unappreciated mechanism by which HIF-1 suppresses FAO to facilitate cancer progression.

Original languageEnglish (US)
Pages (from-to)1930-1942
Number of pages13
JournalCell Reports
Volume8
Issue number6
DOIs
StatePublished - Sep 25 2014

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Acyl-CoA Dehydrogenases
Hypoxia-Inducible Factor 1
Fatty Acids
Oxidation
Acetyl Coenzyme A
Neoplasms
Long-Chain Acyl-CoA Dehydrogenase
Acyl-CoA Dehydrogenase
Liver Neoplasms
Pyruvic Acid
Liver
Tumors
Reactive Oxygen Species
Cells
Switches
Mortality
Oxidoreductases
Growth

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

HIF-1-mediated suppression of acyl-CoA dehydrogenases and fatty acid oxidation is critical for cancer progression. / Huang, De; Li, Tingting; Li, Xinghua; Zhang, Long; Sun, Linchong; He, Xiaoping; Zhong, Xiuying; Jia, Dongya; Song, Libing; Semenza, Gregg L; Gao, Ping; Zhang, Huafeng.

In: Cell Reports, Vol. 8, No. 6, 25.09.2014, p. 1930-1942.

Research output: Contribution to journalArticle

Huang, D, Li, T, Li, X, Zhang, L, Sun, L, He, X, Zhong, X, Jia, D, Song, L, Semenza, GL, Gao, P & Zhang, H 2014, 'HIF-1-mediated suppression of acyl-CoA dehydrogenases and fatty acid oxidation is critical for cancer progression', Cell Reports, vol. 8, no. 6, pp. 1930-1942. https://doi.org/10.1016/j.celrep.2014.08.028
Huang, De ; Li, Tingting ; Li, Xinghua ; Zhang, Long ; Sun, Linchong ; He, Xiaoping ; Zhong, Xiuying ; Jia, Dongya ; Song, Libing ; Semenza, Gregg L ; Gao, Ping ; Zhang, Huafeng. / HIF-1-mediated suppression of acyl-CoA dehydrogenases and fatty acid oxidation is critical for cancer progression. In: Cell Reports. 2014 ; Vol. 8, No. 6. pp. 1930-1942.
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AU - He, Xiaoping

AU - Zhong, Xiuying

AU - Jia, Dongya

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AU - Semenza, Gregg L

AU - Gao, Ping

AU - Zhang, Huafeng

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