D-2-hydroxyglutarate is essential for maintaining oncogenic property of mutant IDH-containing cancer cells but dispensable for cell growth
In: Oncotarget, Jg. 6 (2015-04-20), Heft 11
Online
academicJournal
- 8606 - 8620
Cancer-associated isocitrate dehydrogenase (IDH) 1 and 2 mutations gain a new activity of reducing α-KG to produce D-2-hydroxyglutarate (D-2-HG), which is proposed to function as an oncometabolite by inhibiting α-KG dependent dioxygenases. We investigated the function of D-2-HG in tumorigenesis using IDH1 and IDH2 mutant cancer cell lines. Inhibition of D-2-HG production either by specific deletion of the mutant IDH1-R132C allele or overexpression of D-2-hydroxyglutarate dehydrogenase (D2HGDH) increases α-KG and related metabolites, restores the activity of some α-KG-dependent dioxygenases, and selectively alters gene expression. Ablation of D-2-HG production has no significant effect on cell proliferation and migration, but strongly inhibits anchorage independent growth in vitro and tumor growth in xenografted mouse models. Our study identifies a new activity of oncometabolite D-2-HG in promoting tumorigenesis.
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D-2-hydroxyglutarate is essential for maintaining oncogenic property of mutant IDH-containing cancer cells but dispensable for cell growth
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Autor/in / Beteiligte Person: | Ma, Shenghong ; Jiang, Bowen ; Deng, Wanglong ; Gu, Zhong-Kai ; Wu, Fei-Zhen ; Li, Tingting ; Xia, Yukun ; Yang, Hui ; Ye, Dan ; Xiong, Yue ; Guan, Kun-Liang |
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Zeitschrift: | Oncotarget, Jg. 6 (2015-04-20), Heft 11 |
Veröffentlichung: | eScholarship, University of California, 2015 |
Medientyp: | academicJournal |
Umfang: | 8606 - 8620 |
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