The effects of 2-hydroxyglutarate on the tumorigenesis of gliomas

被引：45

作者：

Reiter-Brennan, Cara ^{[1
]}

Semmler, Lukas ^{[1
]}

Klein, Andreas ^{[1
]}

机构：

[1] Charite Univ Med Berlin, Inst Biochem, Charitepl 1, D-10117 Berlin, Germany

来源：

WSPOLCZESNA ONKOLOGIA-CONTEMPORARY ONCOLOGY | 2018年 / 22卷 / 04期

关键词：

glioblastoma; cancer metabolism; epigenome; IDH1; mutation; 2-hydroxyglutarate;

D O I：

10.5114/wo.2018.82642

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Mutation of the isocitrate-dehydrogenase (IDH) enzymes is one of the central research topics regarding gliomagenesis. Indeed, 70% of gliomas are associated with a gain-of-function IDH mutation and consequently synthesize the oncometabolite, 2-hydroxyglutarate (2-HG). This review aims to elucidate the effects of 2-HG on gliomagenesis. 2-HG promotes tumorigenesis by impacting metabolism, vascularization and altering the epigenome of glioma cells. Glioma metabolism and vascularization is altered by 2-HG's effect on the stability of hypoxia-inducible factor (HIF) and inhibition of endostatin. However, 2-HG's impacts on epigenetic mechanisms are more profound to gliomagenesis. Through competitive inhibition of JHDMs and TET proteins, 2-HG orchestrates histone and DNA hypermethylation, which is associated with gene silencing and dedifferentiation of cells. The hypermethylator phenotype induced by 2-HG also results in alterations of the interaction of the immune system with the tumour. Additionally, this study reviews 2-HG promotion of tumorigenesis by inhibiting repair of DNA alkylation damage through competitive inhibition of AlkB proteins.

引用

页码：215 / 222

页数：8

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