ArticleThe Journal of biological chemistry2022
Expression of gamma-glutamyltransferase 1 in glioblastoma cells confers resistance to cystine deprivation-induced ferroptosis.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- From Gene to Enzyme: Multidimensional Decoding of the GGT Molecular Family and Its Clinical Tumor Diagnosis.Cancer medicine · 2025Pooled it
- Exploit the γ-Glutamyl hydroxymethyl rhodamine green fluorescence in surgical resection: A systematic literature review on clinical indications, fields of application and outcomes.Neurosurgical review · 2025Pooled it
- Nano-formulations in therapeutic strategies targeting cancer ferroptosis.Journal of pharmaceutical analysis · 2026Review
- Ferroptosis and metabolic reprogramming in the immunosuppressive microenvironment of glioblastoma: emerging mechanisms and novel strategies.Frontiers in immunology · 2026Review
- Cardiolipin Dysregulation in Glioblastoma-Effects on Mitochondrial Function Tumor Cell Death and Sensitivity to Mitochondria-Targeting Drugs.Journal of cellular physiology · 2025Review
- Regulation of Ferroptosis in Cancer and Immune Cells.Immune network · 2025Review
- Salidroside can protect against ferroptosis in cardiomyocytes and may be related to the regulation of GGT1.Frontiers in pharmacology · 2025Article
- Amino Acid Deprivation in Glioblastoma: The Role in Survival and the Tumour Microenvironment-A Narrative Review.Biomedicines · 2024Review
- Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of p53 in Glioblastoma Stem Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Glutathione‑degrading enzymes in the complex landscape of tumors (Review).International journal of oncology · 2024Review
- The Cancer Antioxidant Regulation System in Therapeutic Resistance.Antioxidants (Basel, Switzerland) · 2024Review
- The cell biology of ferroptosis.Nature reviews. Molecular cell biology · 2024Review
- Identification of a set of genes potentially responsible for resistance to ferroptosis in lung adenocarcinoma cancer stem cells.Cell death & disease · 2024Article
- Ropivacaine as a novel AKT1 specific inhibitor regulates the stemness of breast cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors.Antioxidants (Basel, Switzerland) · 2024Review
- Targeting ferroptosis opens new avenues in gliomas.International journal of biological sciences · 2024Review
- TXNDC12 inhibits pancreatic tumor cells ferroptosis by regulating GSH/GGT7 and promotes its growth and metastasis.Journal of Cancer · 2024Article
- Mechanism of ferroptosis resistance in cancer cells.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Exploring the causal role of plasma metabolites and metabolite ratios in prostate cancer: a two-sample Mendelian randomization study.Frontiers in molecular biosciences · 2024Article
- Comprehensive insights into the mechanism of keratin degradation and exploitation of keratinase to enhance the bioaccessibility of soybean protein.Biotechnology for biofuels and bioproducts · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis is an iron-dependent mode of cell death caused by excessive oxidative damage to lipids. Lipid peroxidation is normally suppressed by glutathione peroxidase 4, which requires reduced glutathione. Cystine is a major resource for glutathione synthesis, especially in cancer cells. Therefore, cystine deprivation or inhibition of cystine uptake promotes ferroptosis in cancer cells. However, the roles of other molecules involved in cysteine deprivation-induced ferroptosis are unexplored. We report here that the expression of gamma-glutamyltransferase 1 (GGT1), an enzyme that cleaves extracellular glutathione, determines the sensitivity of glioblastoma cells to cystine deprivation-induced ferroptosis at high cell density (HD). In glioblastoma cells expressing GGT1, pharmacological inhibition or deletion of GGT1 suppressed the cell density-induced increase in intracellular glutathione levels and cell viability under cystine deprivation, which were restored by the addition of cysteinylglycine, the GGT product of glutathione cleavage. On the other hand, cystine deprivation induced glutathione depletion and ferroptosis in GGT1-deficient glioblastoma cells even at an HD. Exogenous expression of GGT1 in GGT1-deficient glioblastoma cells inhibited cystine deprivation-induced glutathione depletion and ferroptosis at an HD. This suggests that GGT1 plays an important role in glioblastoma cell survival under cystine-limited and HD conditions. We conclude that combining GGT inhibitors with ferroptosis inducers may provide an effective therapeutic approach for treating glioblastoma.
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