ArticleNeuro-oncology2019
Integrative cross-platform analyses identify enhanced heterotrophy as a metabolic hallmark in glioblastoma.
Article in Neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Gliomas phenocopy an inborn error of metabolism to drive neuronal activity and tumor growth.Cell · 2026Article
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- Stable isotope tracing in human plasma-like medium reveals metabolic and immune modulation of the glioblastoma microenvironment.Neuro-oncology · 2026Article
- Enhanced lipid metabolism serves as a metabolic vulnerability to polyunsaturated fatty acids in glioblastoma.JCI insight · 2026Article
- Identification of urinary metabolic biomarkers for histone 3 lysine27-to-methionine mutation diagnosis in brainstem gliomas.Neuro-oncology · 2025Article
- Metabolomic characterisation of the glioblastoma invasive margin reveals a region-specific signature.Heliyon · 2025Article
- Malignant epithelia cells-derived spermine induces APOE+ macrophages to suppress tumor immunity in adenocarcinoma of the esophagogastric junction.Frontiers in medicine · 2025Article
- Impact of sleep problems on the cardiometabolic risks: an integrated epidemiological and metabolomics study.Diabetology & metabolic syndrome · 2024Article
- Decoding heterogeneous and coordinated tissue architecture in glioblastoma using spatial transcriptomics.iScience · 2024Article
- Metabologenomic characterization uncovers a clinically aggressive IDH mutant glioma subtype.Acta neuropathologica · 2024Article
- Article
- Metabolic checkpoints in glioblastomas: targets for new therapies and non-invasive detection.Frontiers in oncology · 2024Review
- Monitoring central nervous system tumour metabolism using cerebrospinal fluid.Frontiers in oncology · 2024Review
- Metabolomic Profiles of Human Glioma Inform Patient Survival.Antioxidants & redox signaling · 2023Review
- Small molecule metabolites: discovery of biomarkers and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Quinolinate promotes macrophage-induced immune tolerance in glioblastoma through the NMDAR/PPARγ signaling axis.Nature communications · 2023Article
- Sex differences in brain tumor glutamine metabolism reveal sex-specific vulnerabilities to treatment.Med (New York, N.Y.) · 2022Article
- The Comparative Experimental Study of Sodium and Magnesium Dichloroacetate Effects on Pediatric PBT24 and SF8628 Cell Glioblastoma Tumors Using a Chicken Embryo Chorioallantoic Membrane Model and on Cells In Vitro.International journal of molecular sciences · 2022Article
- Distinct metabolic hallmarks of WHO classified adult glioma subtypes.Neuro-oncology · 2022Article
- Effect of Expression of Nuclear-Encoded Cytochrome C Oxidase Subunit 4 Isoforms on Metabolic Profiles of Glioma Cells.Metabolites · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough considerable progress has been made in understanding molecular alterations driving gliomagenesis, the diverse metabolic programs contributing to the aggressive phenotype of glioblastoma remain unclear. The aim of this study was to define and provide molecular context to metabolic reprogramming driving gliomagenesis.
methodsIntegrative cross-platform analyses coupling global metabolomic profiling with genomics in patient-derived glioma (low-grade astrocytoma [LGA; n = 28] and glioblastoma [n = 80]) were performed. Identified programs were then metabolomically, genomically, and functionally evaluated in preclinical models.
resultsClear metabolic programs were identified differentiating LGA from glioblastoma, with aberrant lipid, peptide, and amino acid metabolism representing dominant metabolic nodes associated with malignant transformation. Although the metabolomic profiles of glioblastoma and LGA appeared mutually exclusive, considerable metabolic heterogeneity was observed in glioblastoma. Surprisingly, integrative analyses demonstrated that O6-methylguanine-DNA methyltransferase methylation and isocitrate dehydrogenase mutation status were equally distributed among glioblastoma metabolic profiles. Transcriptional subtypes, on the other hand, tightly clustered by their metabolomic signature, with proneural and mesenchymal tumor profiles being mutually exclusive. Integrating these metabolic phenotypes with gene expression analyses uncovered tightly orchestrated and highly redundant transcriptional programs designed to support the observed metabolic programs by actively importing these biochemical substrates from the microenvironment, contributing to a state of enhanced metabolic heterotrophy. These findings were metabolomically, genomically, and functionally recapitulated in preclinical models.
conclusionDespite disparate molecular pathways driving the progression of glioblastoma, metabolic programs designed to maintain its aggressive phenotype remain conserved. This contributes to a state of enhanced metabolic heterotrophy supporting survival in diverse microenvironments implicit in this malignancy.
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