ArticleOncogene2020
GLS2 is protumorigenic in breast cancers.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Aberrant Energy Metabolism in Tumors and Potential Therapeutic Targets.Genes, chromosomes & cancer · 2024Pooled it
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Metabolic signature of phosphoethanolamine and arginine pathways predicts prognosis and immunotherapy resistance in lung adenocarcinoma.Translational cancer research · 2026Article
- Oxidative Stress Induced Senescent Macrophage-Driven Squamous Cell Carcinoma Invasion via Glutamine Metabolic Reprogramming.Aging cell · 2026Article
- Integrated Proteomic and Metabolomic Analyses Characterise Molecular Alterations Associated with JSRV-Induced OPA.Biology · 2026Article
- Hallmarks of epithelial-mesenchymal plasticity in cancer.Molecular cancer · 2026Review
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- Clinicopathological analysis of GLUT-1, GLS1, and GLS2 expression in breast cancer tissues from Jordanian patients.Scientific reports · 2025Article
- Amino acid metabolism in breast cancer: pathogenic drivers and therapeutic opportunities.Protein & cell · 2025Review
- Machine learning assists regulated cell death crucial biomarker selection in adenocarcinoma of the lung: biological data testing and cell assay determination.Discover oncology · 2025Article
- Interactions between the metabolic reprogramming of liver cancer and tumor microenvironment.Frontiers in immunology · 2025Review
- Drug Repurposing: A Conduit to Unravelling Metabolic Reprogramming for Cancer Treatment.Mini reviews in medicinal chemistry · 2025Review
- Glutaminase inhibition as potential cancer therapeutics: current status and future applications.Journal of enzyme inhibition and medicinal chemistry · 2024Review
- HuR controls glutaminase RNA metabolism.Nature communications · 2024Article
- GLS and GLS2 Glutaminase Isoenzymes in the Antioxidant System of Cancer Cells.Antioxidants (Basel, Switzerland) · 2024Review
- A ferroptosis-related signature predicts the clinical diagnosis and prognosis, and associates with the immune microenvironment of lung cancer.Discover oncology · 2024Article
- Filament formation drives catalysis by glutaminase enzymes important in cancer progression.Nature communications · 2024Article
- Role of glutamine metabolism in tuberculosis pathogenesis: a mini review.Frontiers in tuberculosis · 2024Review
- Targeting amino acid-metabolizing enzymes for cancer immunotherapy.Frontiers in immunology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 6 institutions in 5 countries.
Funding
Abstract
Many types of cancers have a well-established dependence on glutamine metabolism to support survival and growth, a process linked to glutaminase 1 (GLS) isoforms. Conversely, GLS2 variants often have tumor-suppressing activity. Triple-negative (TN) breast cancer (testing negative for estrogen, progesterone, and Her2 receptors) has elevated GLS protein levels and reportedly depends on exogenous glutamine and GLS activity for survival. Despite having high GLS levels, we verified that several breast cancer cells (including TN cells) express endogenous GLS2, defying its role as a bona fide tumor suppressor. Moreover, ectopic GLS2 expression rescued cell proliferation, TCA anaplerosis, redox balance, and mitochondrial function after GLS inhibition by the small molecule currently in clinical trials CB-839 or GLS knockdown of GLS-dependent cell lines. In several cell lines, GLS2 knockdown decreased cell proliferation and glutamine-linked metabolic phenotypes. Strikingly, long-term treatment of TN cells with another GLS-exclusive inhibitor bis-2'-(5-phenylacetamide-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) selected for a drug-resistant population with increased endogenous GLS2 and restored proliferative capacity. GLS2 was linked to enhanced in vitro cell migration and invasion, mesenchymal markers (through the ERK-ZEB1-vimentin axis under certain conditions) and in vivo lung metastasis. Of concern, GLS2 amplification or overexpression is linked to an overall, disease-free and distant metastasis-free worse survival prognosis in breast cancer. Altogether, these data establish an unforeseen role of GLS2 in sustaining tumor proliferation and underlying metastasis in breast cancer and provide an initial framework for exploring GLS2 as a novel therapeutic target.
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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 OpenQuestion graph.