ArticleClinical and translational medicine2024
O-GlcNAcylation promotes malignancy and cisplatin resistance of lung cancer by stabilising NRF2.
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Interplay between NRF2 post-translational modifications and protein-protein interactions: Perspectives from emerging structural and functional evidence.Archives of biochemistry and biophysics · 2026Review
- Serum Starvation Promotes the Proteolysis of OGT by Activating AMPK and the CUL1/SKP1/SKP2 E3 Ubiquitin Ligase in 3T3-L1 Cells.Biomolecules & therapeutics · 2026Article
- miR-941 in extracellular vesicles confers anlotinib resistance via Keap1/Nrf2 axis and represents a therapeutic target in non-small cell lung cancer.Clinical and translational medicine · 2026Article
- Potential oncogenic risks of Keap1-targeting PROTACs: Caution warranted in drug design.Acta pharmaceutica Sinica. B · 2026Article
- The oncogenic signalosome: SQSTM1/p62 as a master integrator of signaling, metabolism, and autophagy in cancer.Toxicological research · 2026Review
- Metabolic drivers of genome instability in cancer: mechanisms and therapeutic opportunities.Experimental hematology & oncology · 2026Review
- Probiotics-enhanced kynurenic acid mitigates cisplatin-induced nephrotoxicity in mice.iScience · 2026Article
- Article
- O-GlcNAcylation at the tumor-immune interface: a metabolic post-translational code driving immune evasion and therapy resistance in cancer.Frontiers in immunology · 2026Review
- O-GlcNAcylation stabilizes RSK4 by antagonizing GSK3β-mediated phosphorylation to enhance radioresistance in esophageal squamous cell carcinoma.International journal of biological sciences · 2026Article
- From sympathetic storm to systemic inflammation: spatiotemporal dynamics of the brain-lung axis in neurogenic pulmonary edema.Frontiers in neuroscience · 2026Review
- Targeting lung cancer: synergistic therapeutic strategy of cuproptosis and immunogenic cell death.Frontiers in cell and developmental biology · 2026Review
- Reducing OGT and O-GlcNAcylation enhance the anticancer effects of oxaliplatin in SW620 metastatic colorectal cancer cells.PloS one · 2026Article
- O-GlcNAcylation levels predict radiotherapy outcome in non-small cell lung cancer.Translational lung cancer research · 2025Article
- Astragalus Polysaccharide Enhances O-GlcNAcylation Through OGT to Improve Intervertebral Disc Degeneration in Rats.Journal of cellular and molecular medicine · 2025Article
- Protein O-GlcNAcylation in Health and Diseases.MedComm · 2025Review
- Understanding O-GlcNAc transferase (OGT): Every amino acid matters.The Journal of biological chemistry · 2025Review
- Article
- Is dolichol pathway dysfunction a significant factor in Alzheimer's disease?Inflammopharmacology · 2025Review
- Crosstalk between O-GlcNAcylation and phosphorylation in metabolism: regulation and mechanism.Cell death and differentiation · 2025Review
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6 authors.
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Abstract
backgroundThe transcription factor NRF2 plays a significant role in regulating genes that protect cells from oxidative damage. O-GlcNAc modification, a type of posttranslational modification, is crucial for cellular response to stress. Although the involvement of both NRF2 and O-GlcNAc in maintaining cellular redox balance and promoting cancer malignancy has been demonstrated, the potential mechanisms remain elusive.
methodsThe immunoblotting, luciferase reporter, ROS assay, co-immunoprecipitation, and immunofluorescence was used to detect the effects of global cellular O-GlcNAcylation on NRF2. Mass spectrometry was utilised to map the O-GlcNAcylation sites on NRF2, which was validated by site-specific mutagenesis and O-GlcNAc enzymatic labelling. Human lung cancer samples were employed to verify the association between O-GlcNAc and NRF2. Subsequently, the impact of NRF2 O-GlcNAcylation in lung cancer malignancy and cisplatin resistance were evaluated in vitro and in vivo.
resultsNRF2 is O-GlcNAcylated at Ser103 residue, which hinders its binding to KEAP1 and thus enhances its stability, nuclear localisation, and transcription activity. Oxidative stress and cisplatin can elevate the phosphorylation of OGT at Thr444 through the activation of AMPK kinase, leading to enhanced binding of OGT to NRF2 and subsequent elevation of NRF2 O-GlcNAcylation. Both in cellular and xenograft mouse models, O-GlcNAcylation of NRF2 at Ser103 promotes the malignancy of lung cancer. In human lung cancer tissue samples, there was a significant increase in global O-GlcNAcylation, and elevated levels of NRF2 and its O-GlcNAcylation compared to paired adjacent normal tissues. Chemotherapy promotes NRF2 O-GlcNAcylation, which in turn decreases cellular ROS levels and drives lung cancer cell survival.
conclusionOur findings indicate that OGT O-GlcNAcylates NRF2 at Ser103, and this modification plays a role in cellular antioxidant, lung cancer malignancy, and cisplatin resistance.
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