ArticleCancer & metabolism2021
Glutaminolysis dynamics during astrocytoma progression correlates with tumor aggressiveness.
Article in Cancer & metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- GLUD1 Inhibition Disrupts Glutamate Homeostasis and Induces Metabolic and Redox Stress in Gliomas.Cells · 2026Article
- Ketogenic diet as a metabolic vehicle enhancing the therapeutic efficacy of mebendazole and devimistat in juvenile syngeneic high-grade glioma.Cell reports. Medicine · 2026Article
- Beyond Glycolysis: Targeting Non-Glycolytic Metabolic Pathways in Brain Tumors for Therapeutic Innovation: A Narrative Review.Health science reports · 2026Article
- HBx-mediated GPT2 suppression promotes liver cancer development by downregulating ADH1A.Cancer biology & medicine · 2026Article
- Targeting distinct amino acid metabolic vulnerabilities in IDH-mutant and IDH-wildtype gliomas.Acta neuropathologica communications · 2025Article
- Oxidative Stress and Antioxidants in Glioblastoma: Mechanisms of Action, Therapeutic Effects and Future Directions.Antioxidants (Basel, Switzerland) · 2025Review
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- Development of a web-based tool for estimating individualized survival curves in glioblastoma using clinical, mRNA, and tumor microenvironment features with fusion techniques.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Glutamine metabolism and ammonia death: targeted modulation for enhanced cancer immunotherapy.Frontiers in immunology · 2025Review
- GLS and GLS2 Glutaminase Isoenzymes in the Antioxidant System of Cancer Cells.Antioxidants (Basel, Switzerland) · 2024Review
- Two Faces of Glutaminase GLS2 in Carcinogenesis.Cancers · 2023Review
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- Intraoperative detection of IDH-mutant glioma using fluorescence lifetime imaging.Journal of biophotonics · 2023Article
- A Novel Cuprotosis-Related lncRNA Signature Effectively Predicts Prognosis in Glioma Patients.Journal of molecular neuroscience : MN · 2023Article
- Heterogeneity of Amino Acid Profiles of Proneural and Mesenchymal Brain-Tumor Initiating Cells.International journal of molecular sciences · 2023Article
- Glutamine metabolism-related genes predict prognosis and reshape tumor microenvironment immune characteristics in diffuse gliomas.Frontiers in neurology · 2023Article
- Glioma‑neuronal interactions in tumor progression: Mechanism, therapeutic strategies and perspectives (Review).International journal of oncology · 2022Review
- Correlation of Matrisome-Associatted Gene Expressions with LOX Family Members in Astrocytomas Stratified by IDH Mutation Status.International journal of molecular sciences · 2022Article
- MFrontiers in genetics · 2022Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundGlioblastoma is the most frequent and high-grade adult malignant central nervous system tumor. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. Metabolic reprogramming currently is recognized as one of the hallmarks of cancer. Glutamine metabolism through glutaminolysis has been associated with tumor cell maintenance and survival, and with antioxidative stress through glutathione (GSH) synthesis.
methodsIn the present study, we analyzed the glutaminolysis-related gene expression levels in our cohort of 153 astrocytomas of different malignant grades and 22 non-neoplastic brain samples through qRT-PCR. Additionally, we investigated the protein expression profile of the key regulator of glutaminolysis (GLS), glutamate dehydrogenase (GLUD1), and glutamate pyruvate transaminase (GPT2) in these samples. We also investigated the glutathione synthase (GS) protein profile and the GSH levels in different grades of astrocytomas. The differential gene expressions were validated in silico on the TCGA database.
resultsWe found an increase of glutaminase isoform 2 gene (GLSiso2) expression in all grades of astrocytoma compared to non-neoplastic brain tissue, with a gradual expression increment in parallel to malignancy. Genes coding for GLUD1 and GPT2 expression levels varied according to the grade of malignancy, being downregulated in glioblastoma, and upregulated in lower grades of astrocytoma (AGII-AGIII). Significant low GLUD1 and GPT2 protein levels were observed in the mesenchymal subtype of GBM.
conclusionsIn glioblastoma, particularly in the mesenchymal subtype, the downregulation of both genes and proteins (GLUD1 and GPT2) increases the source of glutamate for GSH synthesis and enhances tumor cell fitness due to increased antioxidative capacity. In contrast, in lower-grade astrocytoma, mainly in those harboring the IDH1 mutation, the gene expression profile indicates that tumor cells might be sensitized to oxidative stress due to reduced GSH synthesis. The measurement of GLUD1 and GPT2 metabolic substrates, ammonia, and alanine, by noninvasive MR spectroscopy, may potentially allow the identification of IDH1
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