ArticleProceedings of the National Academy of Sciences of the United States of America2024
Activation of polyamine catabolism promotes glutamine metabolism and creates a targetable vulnerability in lung cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Glutamine-driven metabolic reprogramming promotes CAR-T cell function through mTOR-SREBP2 mediated HMGCS1 upregulation in ovarian cancer.Journal of translational medicine · 2025Trial
- Integrative analysis of polyamine-associated genes reveals a prognostic and immunological signature in esophageal squamous cell carcinoma.Discover oncology · 2026Article
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Inhibition of glutamine metabolism blocks tumor growth and sensitizes ccRCC to immune checkpoint blockade.Journal of translational medicine · 2026Article
- Article
- The functional roles and mechanisms of polyamines in age-related bone diseases.Cellular and molecular life sciences : CMLS · 2025Review
- Metabolic support protects mucosa from ferroptosis in radiation-induced mucositis.Nature communications · 2025Article
- Targeting polyamine metabolism and ferroptosis enhances the efficacy of KRAS-targeted therapy depending on KEAP1 status.Nature communications · 2025Article
- [Metabolic reprogramming by glutathione S-transferase enhances environmental adaptation ofHua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2025Article
- Dauricine Overcomes Osimertinib Resistance in Lung Cancer by Inducing Ferroptosis via Stabilizing SAT1.Cancer science · 2025Article
- Receptor-Mediated Internalization of L-Asparaginase into Tumor Cells Is Suppressed by Polyamines.International journal of molecular sciences · 2025Article
- Targeting Spermine Oxidase to Mitigate Traumatic Brain Injury Pathology in the Aging Brain.Antioxidants (Basel, Switzerland) · 2025Article
- Hydrogen sulfide (H2S) coordinates redox balance, carbon metabolism, and mitochondrial bioenergetics to suppress SARS-CoV-2 infection.PLoS pathogens · 2025Article
- A noncanonical role of SAT1 enables anchorage independence and peritoneal metastasis in ovarian cancer.Nature communications · 2025Article
- Bee Pollen Potential to Modulate Ferroptosis: Phytochemical Insights for Age-Related Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Differential Expression of ARG1 and MRC2 in Retinal Müller Glial Cells During Autoimmune Uveitis.Biomolecules · 2025Article
- Spatially-resolved characterization of the metabolic andRSC advances · 2025Article
- Synergistic effect of regorafenib with aminoglycosides in ferroptosis-mediated liver injury.Frontiers in pharmacology · 2025Article
- Glutamine's double-edged sword: fueling tumor growth and offering therapeutic hope.Frontiers in immunology · 2025Review
- Crosstalk between metabolic reprogramming and microbiota: implications for cancer progression and novel therapeutic opportunities.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Polyamines are a class of small polycationic alkylamines that play essential roles in both normal and cancer cell growth. Polyamine metabolism is frequently dysregulated and considered a therapeutic target in cancer. However, targeting polyamine metabolism as monotherapy often exhibits limited efficacy, and the underlying mechanisms are incompletely understood. Here we report that activation of polyamine catabolism promotes glutamine metabolism, leading to a targetable vulnerability in lung cancer. Genetic and pharmacological activation of spermidine/spermine N1-acetyltransferase 1 (SAT1), the rate-limiting enzyme of polyamine catabolism, enhances the conversion of glutamine to glutamate and subsequent glutathione (GSH) synthesis. This metabolic rewiring ameliorates oxidative stress to support lung cancer cell proliferation and survival. Simultaneous glutamine limitation and SAT1 activation result in ROS accumulation, growth inhibition, and cell death. Importantly, pharmacological inhibition of either one of glutamine transport, glutaminase, or GSH biosynthesis in combination with activation of polyamine catabolism synergistically suppresses lung cancer cell growth and xenograft tumor formation. Together, this study unveils a previously unappreciated functional interconnection between polyamine catabolism and glutamine metabolism and establishes cotargeting strategies as potential therapeutics in lung cancer.
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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.