ArticleCell death and differentiation2019
Inhibition of EZH2 induces NK cell-mediated differentiation and death in muscle-invasive bladder cancer.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 91 citations in OpenAlex.
- Comparison of SOX and CAPOX in patients with advanced gastric cancer after laparoscopic D2 gastrectomy: A randomized controlled trial.Cancer medicine · 2024Trial
- Epigenetic reprogramming of lineage switching in cancer.FEBS letters · 2026Review
- Effects of ALDH2 gene expression on the oxidative stress‑mediated NF‑κB/mTOR pathway in ketamine‑induced cystitis.Molecular medicine reports · 2026Article
- Prevalence of KDM6A deficiency in human cancer: A tissue microarray study on 18,570 cancers from 153 different tumor types.Virchows Archiv : an international journal of pathology · 2026Article
- Unraveling the Interplay Between Alcohol, Immunity, and Gastric Cancer: A Genomic Approach.Food science & nutrition · 2025Article
- Lysine demethylases 6 A and 6B as epigenetic regulators in therapeutic resistance of cancer.Clinical epigenetics · 2025Review
- Targeting EZH2 in autoimmune diseases: unraveling epigenetic regulation and therapeutic potential.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Pathway-based cancer transcriptome deciphers a high-resolution intrinsic heterogeneity within bladder cancer classification.Journal of translational medicine · 2025Article
- KDM6A expression loss is frequent in low grade non-invasive urothelial carcinomas of the urinary bladder.Pathologica · 2025Article
- Tracing the Evolution of Sex Hormones and Receptor-Mediated Immune Microenvironmental Differences in Prostate and Bladder Cancers: From Embryonic Development to Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Current advances and future directions in targeting histone demethylases for cancer therapy.Molecules and cells · 2025Review
- Epigenetic regulation of bladder cancer in the context of aging.Frontiers in pharmacology · 2025Review
- Inhibition of KDM4A restricts SQLE transcription and induces oxidative stress imbalance to suppress bladder cancer.Redox biology · 2024Article
- The role of TERT C228T and KDM6A alterations and TME in NMIBC treated with BCG.NPJ precision oncology · 2024Article
- KDM3A Ablation Activates Endogenous Retrovirus Expression to Stimulate Antitumor Immunity in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Targeting histone modifiers in bladder cancer therapy - preclinical and clinical evidence.Nature reviews. Urology · 2024Review
- Review
- Retinoids and EZH2 inhibitors cooperate to orchestrate anti-oncogenic effects on bladder cancer cells.Cancer gene therapy · 2024Article
- Multiomics profiling of urothelial carcinomaiScience · 2024Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Lysine-specific demethylase 6A (KDM6A) and members of the Switch/Sucrose Non-Fermentable (SWI/SNF) family are known to counteract the activity of Enhancer of Zeste Homolog 2 (EZH2), which is often overexpressed and is associated with poor prognosis in muscle-invasive bladder cancer. Here we provide evidence that alterations in chromatin modifying enzymes, including KDM6A and members of the SWI/SNF complex, are frequent in muscle-invasive bladder cancer. We exploit the loss of function mutations in KDM6A and SWI/SNF complex to make bladder cancer cells susceptible to EZH2-based epigenetic therapy that activates an immune response to drive tumor cell differentiation and death. We reveal a novel mechanism of action of EZH2 inhibition, alone and in combination with cisplatin, which induces immune signaling with the largest changes observed in interferon gamma (IFN-γ). This upregulation is a result of activated natural killer (NK) signaling as demonstrated by the increase in NK cell-associated genes MIP-1α, ICAM1, ICAM2, and CD86 in xenografts treated with EZH2 inhibitors. Conversely, EZH2 inhibition results in decreased expression of pluripotency markers, ALDH2 and CK5, and increased cell death. Our results reveal a novel sensitivity of muscle-invasive bladder cancer cells with KMD6A and SWI/SNF mutations to EZH2 inhibition alone and in combination with cisplatin. This sensitivity is mediated through increased NK cell-related signaling resulting in tumor cell differentiation and cell death.
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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.