ArticleJournal of experimental & clinical cancer research : CR2022
OTUD4-mediated GSDME deubiquitination enhances radiosensitivity in nasopharyngeal carcinoma by inducing pyroptosis.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 74 citations in OpenAlex.
- Programmed cell death in inflammation: interactions and holistic perspective.Cellular & molecular immunology · 2026Review
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- ADAR1 regulates radiosensitivity in ESCC through cIAP2-NF-κB signaling and C16orf46 editing.iScience · 2026Article
- Gasdermin E: Bridging Pyroptosis, Immunity, and Disease Pathogenesis Toward Precision Intervention.The protein journal · 2026Review
- Linking deubiquitination to pyroptosis: new perspectives from OTUB1 in hepatocellular carcinoma.Journal of gastrointestinal oncology · 2026Article
- MYBL2 impedes cisplatin sensitivity through suppressing GSDME-mediated pyroptosis in lung adenocarcinoma.Cell death discovery · 2026Article
- Activation of NF-κB signaling pathway in GSDME-low esophageal squamous cell carcinoma cells enhances radioresistance.Journal of translational medicine · 2026Article
- A Ubiquitination-Related Gene Prognostic Signature and the Oncogenic Role of RNF149 in Nasopharyngeal Carcinoma: scRNAseq- Based Bioinformatics and Experimental Validation.Current medicinal chemistry · 2026Article
- Glycolytic Reprogramming Mediated by the OTUD4-FXR1-HIF1A Axis Drives Gastric Cancer Progression.International journal of biological sciences · 2026Article
- Hollow spiky MnOx nanocarriers amplify radiotherapy-induced pyroptosis for eliciting antitumor immunity.Journal of nanobiotechnology · 2025Article
- Vinburnine Sensitizes Radiotherapy Efficacy in Nasopharyngeal Carcinoma by Triggering Pyroptosis and Immune Responses via Activation of EDAR-NFκB Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- OTUD4 suppresses colorectal cancer progression through deubiquitinating p53.Discover oncology · 2025Article
- Suppression of OTUD4 protects against myocardial ischemia-reperfusion injury by increasing autophagic flux and inhibiting apoptosis in cardiomyocytes.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Nicotinamide riboside attenuates radiation-induced intestinal injury by suppressing gasdermin E-mediated pyroptosis in intestinal epithelial cells.Journal of translational medicine · 2025Article
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- Multifunctional nanoagent for enhanced cancer radioimmunotherapy via pyroptosis and cGAS-STING activation.Journal of nanobiotechnology · 2025Article
- Combining decitabine with radiotherapy to enhance nasopharyngeal carcinoma radiosensitivity via the TFAP2C-OTUD1-SLC25A11 axis.Cell death & disease · 2025Article
- The Role and Mechanism of GSDME-Dependent Pyroptosis in Cochlear Marginal Cells Injury by Cisplatin.Biomedicines · 2025Article
- Nuclear receptors as novel regulators that modulate cancer radiosensitivity and normal tissue radiotoxicity.Molecular cancer · 2025Review
- NAP1L1 degradation by FBXW7 reduces the deubiquitination of HDGF-p62 signaling to stimulate autophagy and induce primary cisplatin chemosensitivity in nasopharyngeal carcinoma.Molecular cancer · 2025Article
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRadioresistance is the primary cause of nasopharyngeal carcinoma (NPC) treatment failure. Previous studies have focused on the deficits in cellular apoptosis as a mechanism for radioresistance; however, additional potential death modes involved in modulating radiosensitivity of NPC have not been explored.
methodsPyroptosis was assessed by phase-contrast imaging, LDH release assays, live cell imaging, and Western blotting. In vitro and in vivo assays were used to investigate the function of gasdermin E (GSDME) and ovarian tumor family deubiquitinase 4 (OTUD4). NPC tissues were analyzed using Western blotting, immunohistochemistry, and real-time PCR. The molecular mechanism was determined using immunoprecipitation assays and mass spectrometry.
resultsLive cell imaging revealed that 40-75% of irradiation-induced dead NPC cells were pyroptotic cells. Furthermore, irradiation-induced pyroptosis is triggered by GSDME, which are cleaved by activated caspase-3 in the intrinsic mitochondrial pathway. Additionally, GSDME was significantly downregulated in radioresistant NPC specimens. Low GSDME expression was a predictor of worse prognosis and conferred NPC radioresistance both in vitro and in vivo. Mechanistically, OTUD4 deubiquitinated and stabilized GSDME, enhancing radiosensitivity of NPC cells by promoting pyroptosis. Clinically, OTUD4 was significantly correlated with GSDME in NPC biopsies, and patients with low expression of both OTUD4 and GSDME suffered the worst radiotherapy response and survival.
conclusionsGSDME-dependent pyroptosis is a critical determinant of radiosensitivity in NPC, and is modulated by OTUD4 via deubiquitinating and stabilizing GSDME. These findings reveal a promising novel direction to investigate radioresistance and suggest potential therapeutic targets for sensitizing NPC to radiotherapy.
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