ArticleCell death & disease2021
Rewiring of purine metabolism in response to acidosis stress in glioma stem cells.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- A novel cuproptosis-related prognostic gene signature is identified by machine learning and integrative analyses in gliomas.Molecular and cellular biochemistry · 2026Article
- Metabolic Landscape and Emerging Therapeutic Potential in Pediatric and Adult Gliomas.International journal of molecular sciences · 2026Review
- The symbiotic axis between the acidic tumor microenvironment and cancer stem cells: a driver of malignancy and therapeutic resistance.Frontiers in oncology · 2026Review
- Glioblastoma: From Pathophysiology to Novel Therapeutic Approaches.Biomedicines · 2025Review
- A pH-responsive PEG coating strategy for enhancing the enrichment of small extracellular vesicles towards disease regions with acidic microenvironment.Materials today. Bio · 2025Article
- PAICS-Driven Purine Biosynthesis and Its Prognostic Implications in Lung Adenocarcinoma: A Novel Risk Stratification Model and Therapeutic Insights.Current issues in molecular biology · 2025Article
- Glutathione Dynamics in the Tumor Microenvironment: A Potential Target of Cancer Stem Cells and T Cells.International journal of stem cells · 2024Review
- XPO1 inhibition displays anti-leukemia efficacy against DNMT3A-mutant acute myeloid leukemia via downregulating glutathione pathway.Annals of hematology · 2024Article
- Glucose metabolism in B cell malignancies: a focus on glycolysis branching pathways.Molecular oncology · 2024Review
- Immune cell infiltration and drug response in glioblastoma multiforme: insights from oxidative stress-related genes.Cancer cell international · 2024Article
- Inhibition of epigenetic and cell cycle-related targets in glioblastoma cell lines reveals that onametostat reduces proliferation and viability in both normoxic and hypoxic conditions.Scientific reports · 2024Article
- Identification and validation of potential prognostic biomarkers in glioblastoma via the mesenchymal stem cell infiltration level.Frontiers in oncology · 2024Article
- Bridging the gap: advancing cancer cell culture to reveal key metabolic targets.Frontiers in oncology · 2024Review
- Review
- Metabolic Modeling Identifies a Novel Molecular Type of Glioblastoma Associated with Good Prognosis.Metabolites · 2023Article
- MicroRNA-21 guide and passenger strand regulation of adenylosuccinate lyase-mediated purine metabolism promotes transition to an EGFR-TKI-tolerant persister state.Cancer gene therapy · 2022Article
- Mitochondrial ROS signalling requires uninterrupted electron flow and is lost during ageing in flies.GeroScience · 2022Article
- Elevated Hexose-6-Phosphate Dehydrogenase Regulated by OSMR-AS1/hsa-miR-516b-5p Axis Correlates with Poor Prognosis and Dendritic Cells Infiltration of Glioblastoma.Brain sciences · 2022Article
- Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation.International journal of molecular sciences · 2022Article
- Production and Stabilization of Specific Upregulated Long Noncoding RNA HOXD-AS2 in Glioblastomas Are Mediated by TFE3 and miR-661, Respectively.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioma stem cells (GSCs) contribute to therapy resistance and poor outcomes for glioma patients. A significant feature of GSCs is their ability to grow in an acidic microenvironment. However, the mechanism underlying the rewiring of their metabolism in low pH remains elusive. Here, using metabolomics and metabolic flux approaches, we cultured GSCs at pH 6.8 and pH 7.4 and found that cells cultured in low pH exhibited increased de novo purine nucleotide biosynthesis activity. The overexpression of glucose-6-phosphate dehydrogenase, encoded by G6PD or H6PD, supports the metabolic dependency of GSCs on nucleotides when cultured under acidic conditions, by enhancing the pentose phosphate pathway (PPP). The high level of reduced glutathione (GSH) under acidic conditions also causes demand for the PPP to provide NADPH. Taken together, upregulation of G6PD/H6PD in the PPP plays an important role in acidic-driven purine metabolic reprogramming and confers a predilection toward glioma progression. Our findings indicate that targeting G6PD/H6PD, which are closely related to glioma patient survival, may serve as a promising therapeutic target for improved glioblastoma therapeutics. An integrated metabolomics and metabolic flux analysis, as well as considering microenvironment and cancer stem cells, provide a precise insight into understanding cancer metabolic reprogramming.
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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 Socratic graph.