ArticleCancer research2024
Therapeutic Targeting of the GLS1-c-Myc Positive Feedback Loop Suppresses Glutaminolysis and Inhibits Progression of Head and Neck Cancer.
Article in Cancer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Metabolites and cancer metastasis.Oncogene · 2026Review
- Reversing Macrophage Immunometabolic Dysfunction in Prolonged Infections Via a Glutaminolysis-Fueled Restoration-Based Hierarchically Selective Therapeutic System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecular Mechanisms and Therapeutic Targeting of the Macrophage Metabolic-Epigenetic Interaction Network in Chronic Obstructive Pulmonary Disease.Cell biochemistry and biophysics · 2026Review
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Plumbagin Is a PKM2 Activator That Modulates Glutamine Metabolism and Dependency in Leukemia.Metabolites · 2026Article
- MYC in Oncogenesis and Therapeutic Implications.MedComm · 2026Review
- Metabolic Reprogramming in Oral Cancer: A Narrative Review of Therapeutic Perspectives with Emphasis on Dichloroacetate.Current issues in molecular biology · 2026Review
- GLS1 Orchestrates Exosome-Mediated Tumor-Endothelial Communication to Facilitate Angiogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rewiring tumor metabolism: heterogeneity, oncometabolites, and adaptive plasticity.Experimental hematology & oncology · 2026Review
- Metabolomic Insights into Head and Neck Cancer: Recent Advances and Future Directions.Current oncology (Toronto, Ont.) · 2026Review
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Amino Acid Metabolic Enzymes in Gastric Cancer: Roles and Mechanisms in Tumorigenesis and Progression.Oncology research · 2026Review
- Tumor Microenvironment-Responsive Nanoparticles for Pancreatic Cancer Imaging and Treatment.International journal of nanomedicine · 2026Review
- Mechanical stress, metabolic reprogramming and stromal remodeling: an emerging paradigm in the bladder cancer mechano-micro-environment.Frontiers in genetics · 2026Review
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- The Interdependence of Carbon Substrates and Metabolic Pathways Enables the Metabolic Plasticity of Cancer Cells.Advances in experimental medicine and biology · 2026Review
- Article
- Review
- Glutamine: a new strategy for targeted metabolic therapy in the tumor microenvironment.Cell death discovery · 2025Review
- Comprehensive analysis of ammonia-induced cell death and GLS1 in gastric adenocarcinoma: implications for prognosis and therapeutic strategies.Cancer cell international · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Head and neck squamous cell carcinoma (HNSCC) is addicted to glutaminolysis. Targeting this metabolic dependency has emerged as a potential therapeutic approach for HNSCC. In this study, we conducted a bioinformatic analysis of The Cancer Genome Atlas HNSCC cohort that revealed a robust correlation between expression of MYC (encoding the protein c-Myc) and glutaminase 1 (GLS1), which catalyzes the first step in glutaminolysis. Intriguingly, disruption of GLS1 signaling in HNSCC cells by genetic depletion or CB-839 treatment resulted in a reduction in c-Myc protein stability via a ubiquitin-specific peptidase 1-dependent ubiquitin-proteasome pathway. On the other hand, c-Myc directly binds to the promoter region of GLS1 and upregulates its transcription. Notably, the GLS1-c-Myc pathway enhanced acetyl-coenzyme A carboxylase-dependent Slug acetylation, prompting cancer cell invasion and metastasis. Thus, the GLS1-c-Myc axis emerged as a positive feedback loop critical for driving the aggressiveness of HNSCC. Therapeutically, combining CB-839 with the c-Myc inhibitor MYCi975 strongly suppressed GLS1-c-Myc signaling, resulting in a superior antitumor effect compared with either single agent in an orthotopic mouse model of HNSCC. These findings hold promise for the development of effective therapies for patients with HNSCC, addressing an urgent need arising from the significant incidence and high metastatic rate of the disease. Significance: GLS1 and c-Myc form a positive feedback loop that promotes head and neck cancer metastasis and can be targeted as a promising therapeutic strategy for this disease.
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