ArticleOncotarget2015
D-2-hydroxyglutarate is essential for maintaining oncogenic property of mutant IDH-containing cancer cells but dispensable for cell growth.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Metabolic rewiring of the tumor microenvironment: therapeutic intervention of multi-pathway adaptations to impede cancer metastasis.Frontiers in molecular biosciences · 2026Review
- Stereochemistry and Charged State Influence Effector Outcomes of d-2-Hydroxyglutarate Dehydrogenase Ligands.Biochemistry · 2025Article
- Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor models.The Journal of biological chemistry · 2025Article
- Detection and analysis of chiral molecules as disease biomarkers.Nature reviews. Chemistry · 2023Review
- Isocitrate dehydrogenase (IDH) mutant gliomas: A Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions.Neuro-oncology · 2023Article
- Clinical usefulness of 2-hydroxyglutarate as a biomarker in IDH-mutant chondrosarcoma.Journal of bone oncology · 2022Article
- Metabolic adaptations in cancers expressing isocitrate dehydrogenase mutations.Cell reports. Medicine · 2021Review
- The Inhibition of B7H3 by 2-HG Accumulation Is Associated With Downregulation of VEGFA in IDH Mutated Gliomas.Frontiers in cell and developmental biology · 2021Article
- An acidic residue buried in the dimer interface of isocitrate dehydrogenase 1 (IDH1) helps regulate catalysis and pH sensitivity.The Biochemical journal · 2020Article
- Article
- The oncometabolite 2-hydroxyglutarate produced by mutant IDH1 sensitizes cells to ferroptosis.Cell death & disease · 2019Article
- Characterization of cancer-associated IDH2 mutations that differ in tumorigenicity, chemosensitivity and 2-hydroxyglutarate production.Oncotarget · 2019Article
- Mutation of IDH1 aggravates the fatty acid‑induced oxidative stress in HCT116 cells by affecting the mitochondrial respiratory chain.Molecular medicine reports · 2019Article
- Rapid diagnosis of IDH1-mutated gliomas by 2-HG detection with gas chromatography mass spectrometry.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Vascular-endothelial response to IDH1 mutant fibrosarcoma secretome and metabolite: implications on cancer microenvironment.American journal of cancer research · 2019Article
- Advances in Brain Cancer: Creating Monoallelic Single Point Mutation in IDH1 by Single Base Editing.Journal of oncology research and therapy · 2019Article
- Contribution of the Wnt Pathway to Defining Biology of Glioblastoma.Neuromolecular medicine · 2018Review
- Oncogenic R132 IDH1 Mutations Limit NADPH for De Novo Lipogenesis through (D)2-Hydroxyglutarate Production in Fibrosarcoma Sells.Cell reports · 2018Article
- Heterozygous IDH1Oncogene · 2018Article
- Molecular evaluation of a sporadic paraganglioma with concurrent IDH1 and ATRX mutations.Endocrine · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.