ArticleWorld journal of stem cells2020
Glutathione metabolism is essential for self-renewal and chemoresistance of pancreatic cancer stem cells.
Article in World journal of stem cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 68 citations in OpenAlex.
- m6A Modification-Mediated LINC01547 Promotes Pancreatic Cancer Growth and Gemcitabine Resistance Through miR-34a-5p/MYH9 Axis.Biochemical genetics · 2026Article
- GPX8Oncogene · 2026Article
- Redox-active nitroxides enhance cisplatin efficacy against cervical cancer.Redox biology · 2026Article
- Co-expression of cancer stem cell markers CD24 and CD133 in gastric cancer tissues: Clinicopathological and prognostic significance.World journal of stem cells · 2026Article
- Carbonic Anhydrase Inhibitors in Oncology.Sub-cellular biochemistry · 2026Review
- Ferroptosis-Based Nanotherapy for Pancreatic Ductal Adenocarcinoma Through Glutathione Depletion and Iron Accumulation.International journal of nanomedicine · 2026Review
- Glutathione-associated redox regulation alleviates radio-resistance of canine cancer stem-like cells with low proteasome activity.Scientific reports · 2025Article
- Integrated molecular and microenvironmental drivers of drug resistance in gastrointestinal cancers: mechanisms, immunotherapy challenges, and precision strategies.Frontiers in oncology · 2025Review
- Drug combination discovery assisted by AI and untargeted metabolomics: pamiparib and anlotinib synergistic potentiation for ovarian cancer treatment.Frontiers in pharmacology · 2025Article
- Integrated cytomembrane proteomics identifies EpCAM/MGST1 as therapeutic targets in metastatic laryngeal carcinoma.Frontiers in genetics · 2025Article
- Integrative single-cell RNA sequencing and bulk RNA sequencing reveals the characteristics of glutathione metabolism and protective role of GSTA4 gene in pancreatic cancer.Frontiers in immunology · 2025Article
- Glutathione Dynamics in the Tumor Microenvironment: A Potential Target of Cancer Stem Cells and T Cells.International journal of stem cells · 2024Review
- Fatty acid oxidation is critical for the tumorigenic potential and chemoresistance of pancreatic cancer stem cells.Journal of translational medicine · 2024Article
- Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Role of reactive oxygen species in myelodysplastic syndromes.Cellular & molecular biology letters · 2024Review
- Glutathione Reductase Expression and Its Prognostic Significance in Colon Cancer.International journal of molecular sciences · 2024Article
- A Prognostic Activity of Glutaredoxin 1 Protein (Grx1) in Colon Cancer.International journal of molecular sciences · 2024Article
- Glutathione and Xanthine Metabolic Changes in Tamoxifen Resistant Breast Cancer Cell Lines are Mediated by Down-Regulation ofJournal of Cancer · 2024Article
- PTC596-Induced BMI-1 Inhibition Fights Neuroblastoma Multidrug Resistance by Inducing Ferroptosis.Antioxidants (Basel, Switzerland) · 2023Article
- GPX8 deficiency-induced oxidative stress reprogrammed m6A epitranscriptome of oral cancer cells.Epigenetics · 2023Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCellular metabolism regulates stemness in health and disease. A reduced redox state is essential for self-renewal of normal and cancer stem cells (CSCs). However, while stem cells rely on glycolysis, different CSCs, including pancreatic CSCs, favor mitochondrial metabolism as their dominant energy-producing pathway. This suggests that powerful antioxidant networks must be in place to detoxify mitochondrial reactive oxygen species (ROS) and maintain stemness in oxidative CSCs. Since glutathione metabolism is critical for normal stem cell function and CSCs from breast, liver and gastric cancer show increased glutathione content, we hypothesized that pancreatic CSCs also rely on this pathway for ROS detoxification.
aimTo investigate the role of glutathione metabolism in pancreatic CSCs.
methodsPrimary pancreatic cancer cells of patient-derived xenografts (PDXs) were cultured in adherent or CSC-enriching sphere conditions to determine the role of glutathione metabolism in stemness. Real-time polymerase chain reaction (PCR) was used to validate RNAseq results involving glutathione metabolism genes in adherent
resultsAnalysis of our previously published RNAseq dataset E-MTAB-3808 revealed up-regulation of genes involved in the KEGG (Kyoto Encyclopedia of Genes and Genomes) Pathway Glutathione Metabolism in CSC-enriched cultures compared to their differentiated counterparts. Consistently, in pancreatic cancer patient samples the expression of most of these up-regulated genes positively correlated with a stemness signature defined by
conclusionOur data suggest that pancreatic CSCs depend on glutathione metabolism. Pharmacological targeting of this pathway showed that high GSH content is essential to maintain CSC functionality in terms of self-renewal and chemoresistance.
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