ArticleCancer & metabolism2018
Mutant IDH1 gliomas downregulate phosphocholine and phosphoethanolamine synthesis in a 2-hydroxyglutarate-dependent manner.
Article in Cancer & metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Case Report: Metabolic alterations and cholesterol esterification in a low-grade diffuse astrocytoma patient who progressed to glioblastoma at recurrence.Frontiers in oncology · 2025Article
- Assessing the Metabolic Variations of Invasive and Noninvasive Unilateral Retinoblastoma Patients.ACS omega · 2024Article
- Review
- Dissecting causal relationships between gut microbiota, blood metabolites, and glioblastoma multiforme: a two-sample Mendelian randomization study.Frontiers in microbiology · 2024Article
- The curious case of IDH mutant acute myeloid leukaemia: biochemistry and therapeutic approaches.Biochemical Society transactions · 2023Review
- Review
- Lipid Alterations in Glioma: A Systematic Review.Metabolites · 2022Review
- Deuterium Metabolic Imaging Reports on TERT Expression and Early Response to Therapy in Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Deuterium magnetic resonance spectroscopy enables noninvasive metabolic imaging of tumor burden and response to therapy in low-grade gliomas.Neuro-oncology · 2022Article
- WNT/β-Catenin-Mediated Resistance to Glucose Deprivation in Glioblastoma Stem-like Cells.Cancers · 2022Article
- Acquisition and quantification pipeline for in vivo hyperpolarizedMagnetic resonance in medicine · 2022Article
- Grading of endometrial cancer usingScientific reports · 2021Article
- Metabolic imaging detects elevated glucose flux through the pentose phosphate pathway associated with TERT expression in low-grade gliomas.Neuro-oncology · 2021Article
- From the (Epi)Genome to Metabolism and Vice Versa; Examples from Hematologic Malignancy.International journal of molecular sciences · 2021Review
- Choline Kinase: An Unexpected Journey for a Precision Medicine Strategy in Human Diseases.Pharmaceutics · 2021Review
- Magnetic resonance spectroscopy for the study of cns malignancies.Progress in nuclear magnetic resonance spectroscopy · 2021Article
- The metabolic reprogramming in acute myeloid leukemia patients depends on their genotype and is a prognostic marker.Blood advances · 2021Article
- Non-invasive assessment of telomere maintenance mechanisms in brain tumors.Nature communications · 2021Article
- The Roles of 2-Hydroxyglutarate.Frontiers in cell and developmental biology · 2021Review
- 2-Hydroxyglutarate in Cancer Cells.Antioxidants & redox signaling · 2020Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundMagnetic resonance spectroscopy (MRS) studies have identified elevated levels of the phospholipid precursor phosphocholine (PC) and phosphoethanolamine (PE) as metabolic hallmarks of cancer. Unusually, however, PC and PE levels are reduced in mutant isocitrate dehydrogenase 1 (IDHmut) gliomas that produce the oncometabolite 2-hydroxyglutarate (2-HG) relative to wild-type IDH1 (IDHwt) gliomas. The goal of this study was to determine the molecular mechanism underlying this unusual metabolic reprogramming in IDHmut gliomas.
methodsSteady-state PC and PE were quantified using
resultsDe novo synthesis of PC and PE was reduced in IDHmut cells relative to IDHwt. Concomitantly, CK activity and EK activity were reduced in IDHmut cells. Pharmacological manipulation of 2-HG levels established that 2-HG was responsible for reduced CK activity, EK activity, PC and PE. 2-HG has previously been reported to stabilize levels of HIF-1α, a known regulator of CK activity. Silencing HIF-1α in IDHmut cells restored CK activity, EK activity, PC and PE to IDHwt levels. Our findings were recapitulated in IDHmut orthotopic tumor xenografts and, most importantly, in IDHmut patient biopsies, validating our findings in vivo and in the clinic.
conclusionsThis study identifies, to our knowledge for the first time, a direct role for 2-HG in the downregulation of CK and EK activity, and thereby, PC and PE synthesis in IDHmut gliomas. These results highlight the unusual reprogramming of phospholipid metabolism in IDHmut gliomas and have implications for the identification of MRS-detectable metabolic biomarkers associated with 2-HG status.
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