title: Aberrant IDH3α expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis.
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.
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Kyoto, Japan.|Department of Radiation Medicine, Fourth Military Medical University, Shaanxi, China.
authors.forename: L
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Kyoto, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Morinibu
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Kyoto, Japan.|Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Kyoto, Japan.|Department of Radiation Medicine, Fourth Military Medical University, Shaanxi, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Kyoto, Japan.
authors.forename: C J
authors.initials: CJ
authors.lastname: Yeom
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Kyoto, Japan.|Department of Radiation Medicine, Fourth Military Medical University, Shaanxi, China.
authors.forename: T
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, Kyoto University, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hirota
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shinomiya
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Itasaka
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Department of Radiation Medicine, Fourth Military Medical University, Shaanxi, China.
authors.forename: G
authors.initials: G
authors.lastname: Guo
authors.affiliation: Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK.
authors.forename: E M
authors.initials: EM
authors.lastname: Hammond
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hiraoka
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Kyoto, Japan.|Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Harada
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D010085:Oxidative Phosphorylation
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007521:Isocitrate Dehydrogenase; D005947:Glucose