ArticleCell death and differentiation2021
USP9X-mediated KDM4C deubiquitination promotes lung cancer radioresistance by epigenetically inducing TGF-β2 transcription.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Peripheral Blood Transcriptomic Profile Associated with Cutaneous Radiation Injury in Cancer Patients Undergoing Radiotherapy.International journal of molecular sciences · 2026Article
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- Reciprocal signaling-metabolic crosstalk between fibroblasts and tumor cells drives cetuximab tolerance in head and neck cancers.Journal of experimental & clinical cancer research : CR · 2026Article
- USP9X regulates copper-induced CASP9/CASP3/GSDME-dependent pyroptosis by deubiquitinating JAK1.Apoptosis : an international journal on programmed cell death · 2026Article
- Global analysis of cancer cell responses to USP9X inhibition.The EMBO journal · 2026Article
- Mechanism of FOXP2 in the Hepatocellular Carcinoma Progression via Ferroptosis Through RBM15B-Mediated m6A Modification.Applied biochemistry and biotechnology · 2026Article
- Role of the Super-Enhancer Component Bromodomain Protein 4 in the Radiation Response of Human Head and Neck Squamous Cell Carcinoma Cells.Current issues in molecular biology · 2026Article
- Geno-guided targeting of ferroptosis: a multi-layered network to overcome radioresistance in lung cancer.Frontiers in cell and developmental biology · 2026Review
- The Lysine Demethylase KDM4C Is an Oncogenic Driver and Regulates ERK Activity in KRAS-Mutant Pancreatic Ductal Adenocarcinoma.Cancer research communications · 2026Article
- Review
- Pathological role of deubiquitinating enzymes in lung cancer: recent insights and advances.American journal of cancer research · 2026Review
- Bibliometrics and potential gene analysis of post-translational modifications in lung cancer.Journal of thoracic disease · 2025Article
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- Molecular Mechanisms of the Ubiquitin-Specific Proteases (USPs) Family in Biliary Tract Cancer and Targeted Intervention Strategies.Biomedicines · 2025Review
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- Phase 1 study of zavondemstat (TACH101), a first-in-class KDM4 inhibitor, in patients with advanced solid tumors.The oncologist · 2025Article
- HDAC6 and USP9X Control Glutamine Metabolism by Stabilizing GS to Promote Glioblastoma Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Radioresistance is regarded as the main barrier to effective radiotherapy in lung cancer. However, the underlying mechanisms of radioresistance remain elusive. Here, we show that lysine-specific demethylase 4C (KDM4C) is overexpressed and correlated with poor prognosis in lung cancer patients. We provide evidence that genetical or pharmacological inhibition of KDM4C impairs tumorigenesis and radioresistance in lung cancer in vitro and in vivo. Moreover, we uncover that KDM4C upregulates TGF-β2 expression by directly reducing H3K9me3 level at the TGF-β2 promoter and then activates Smad/ATM/Chk2 signaling to confer radioresistance in lung cancer. Using tandem affinity purification technology, we further identify deubiquitinase USP9X as a critical binding partner that deubiquitinates and stabilizes KDM4C. More importantly, depletion of USP9X impairs TGF-β2/Smad signaling and radioresistance by destabilizing KDM4C in lung cancer cells. Thus, our findings demonstrate that USP9X-mediated KDM4C deubiquitination activates TGF-β2/Smad signaling to promote radioresistance, suggesting that targeting KDM4C may be a promising radiosensitization strategy in the treatment of lung cancer.
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Registered trials
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.