ArticleNature metabolism2022
Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- Application of organoid models in basic and translational research of lung cancer: a narrative review.Translational lung cancer research · 2026Review
- Targeting glutamine metabolism to modulate macrophage functions in the tumor microenvironment.Discover oncology · 2026Review
- The APC/C subunit APC7 promotes hepatocellular carcinoma progression by mediating ubiquitination and degradation of LATS1 to activate YAP/TAZ.Biology direct · 2026Article
- Radiation-Enhanced CD24 Membrane Trafficking via GPI Anchoring Mediates Antitumor Immune Evasion.Cancer research · 2026Article
- Glutamine synthetase deficiency enhances CD8 T cell survival and stress resilience in the tumor microenvironment.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Lung cancer organoids for functional precision oncology: from disease modeling to clinical decision support.Frontiers in oncology · 2026Review
- Amino acids metabolism: a potential target for cancer treatment.Molecular cancer · 2025Review
- Glutamine synthetase regulates the changes of vascular permeability in glioma induced by radiotherapy.Medical oncology (Northwood, London, England) · 2025Article
- GLUL mediates FOXO3 O-GlcNAcylation to regulate the osteogenic differentiation of BMSCs and senile osteoporosis.Cell death and differentiation · 2025Article
- Metabolic syndrome-related gene signature for prognosis and immune microenvironment prediction in hepatocellular carcinoma.Scientific reports · 2025Article
- Inhibition of glutamine synthetase enhances hepatocellular carcinoma radiosensitivity through ROS-induced excessive mitophagy.Molecular biology reports · 2025Article
- Glutamine synthetase shields triple-negative breast cancer cells from ferroptosis in metastasis triggered by glutamine deprivation.Breast cancer research : BCR · 2025Article
- HDAC6 and USP9X Control Glutamine Metabolism by Stabilizing GS to Promote Glioblastoma Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PRDX6 Prevents NNMT Ubiquitination and Degradation as a Nonenzymatic Mechanism to Promote Ovarian Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis.MedComm · 2025Review
- Noncanonical UPR factor CREB3L2 drives immune evasion of triple-negative breast cancer through Hedgehog pathway modulation in T cells.Science advances · 2025Article
- Mechanistic study of glutamine metabolic reprogramming driving non-small cell lung cancer progression via the FGF17-FGFR4 axis mediating epithelial-mesenchymal transition.Frontiers in molecular biosciences · 2025Article
- The Role and Treatment Strategies of Ammonia-Related Metabolism in Tumor Microenvironment.Current gene therapy · 2025Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
22 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumors can reprogram the functions of metabolic enzymes to fuel malignant growth; however, beyond their conventional functions, key metabolic enzymes have not been found to directly govern cell mitosis. Here, we report that glutamine synthetase (GS) promotes cell proliferation by licensing mitotic progression independently of its metabolic function. GS depletion, but not impairment of its enzymatic activity, results in mitotic arrest and multinucleation across multiple lung and liver cancer cell lines, patient-derived organoids and xenografted tumors. Mechanistically, GS directly interacts with the nuclear pore protein NUP88 to prevent its binding to CDC20. Such interaction licenses activation of the CDC20-mediated anaphase-promoting complex or cyclosome to ensure proper metaphase-to-anaphase transition. In addition, GS is overexpressed in human non-small cell lung cancer and its depletion reduces tumor growth in mice and increases the efficacy of microtubule-targeted chemotherapy. Our findings highlight a moonlighting function of GS in governing mitosis and illustrate how an essential metabolic enzyme promotes cell proliferation and tumor development, beyond its main metabolic function.
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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 OpenQuestion graph.