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Oncogene. 2015 Sep 3;34(36):4758-66. doi: 10.1038/onc.2014.411. Epub 2014 Dec 22.

Aberrant IDH3α expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis.

Author information

1
Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.
2
Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Kyoto, Japan.
3
Department of Radiation Medicine, Fourth Military Medical University, Shaanxi, China.
4
Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
5
Department of Anesthesia, Kyoto University Hospital, Kyoto University, Kyoto, Japan.
6
Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK.
7
Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan.

Abstract

Cancer cells gain a growth advantage through the so-called Warburg effect by shifting glucose metabolism from oxidative phosphorylation to aerobic glycolysis. Hypoxia-inducible factor 1 (HIF-1) has been suggested to function in metabolic reprogramming; however, the underlying mechanism has not been fully elucidated. We found that the aberrant expression of wild-type isocitrate dehydrogenase 3α (IDH3α), a subunit of the IDH3 heterotetramer, decreased α-ketoglutarate levels and increased the stability and transactivation activity of HIF-1α in cancer cells. The silencing of IDH3α significantly delayed tumor growth by suppressing the HIF-1-mediated Warburg effect and angiogenesis. IDH3α expression was associated with the poor postoperative overall survival of lung and breast cancer patients. These results justify the exploitation of IDH3 as a novel target for the diagnosis and treatment of cancers.

PMID:
25531325
DOI:
10.1038/onc.2014.411
[Indexed for MEDLINE]

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