ArticleCancer research2023
KDM6A Loss Triggers an Epigenetic Switch That Disrupts Urothelial Differentiation and Drives Cell Proliferation in Bladder Cancer.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Multiomic profiling links L1 retrotransposition to genomic instability and ecDNA in bladder cancer.Nature communications · 2026Article
- Review
- 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
- Loss of KDM6A-mediated genomic instability and metabolic reprogramming regulates response to therapeutic perturbations in bladder cancer.Nature communications · 2026Article
- Genomic profile of an IDH-wild-type glioblastoma diagnosed following TNF-α inhibitor therapy: a molecular case study.Frontiers in oncology · 2026Article
- Machine learning-based determination of sex-related bladder cancer biomarkers.Frontiers in bioinformatics · 2026Article
- FAM111B promotes prostate cancer progression by inhibiting apoptosis via ATF3 suppression and MAPK pathway activation: a novel biomarker and therapeutic target.Cancer cell international · 2025Article
- Machine-learning-based determination of sex-related bladder cancer biomarkers.bioRxiv : the preprint server for biology · 2025Article
- Genetic Aberrations in Normal Tissues Adjacent to Biliary Tract Cancers.Biomedicines · 2025Article
- Defensin-Rich Platelets Drive Pro-Tumorigenic Programs in Pancreatic Adenocarcinoma.International journal of molecular sciences · 2025Article
- The Future of Bladder Cancer Therapies: Integrating Hydrogel Scaffolds for Epigenetic Regulator Delivery.Cureus · 2025Review
- DNA Methylation in Bladder Cancer: Diagnostic and Therapeutic Perspectives-A Narrative Review.International journal of molecular sciences · 2025Review
- Integrative Analysis Reveals the Prognostic Effects of Epigenetic Regulators in Bladder Cancer.Cancer medicine · 2025Article
- EZH2 regulates tumor-associated macrophages by the KDM6A-mediated inflammatory response in HPV16-positive cervical cancer.Human cell · 2025Article
- UTX (KDM6A) promotes differentiation noncatalytically in somatic self-renewing epithelia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The interplay between angiogenesis-associated genes and molecular, clinical, and immune features in bladder cancer.Discover oncology · 2025Article
- Androgen receptor signalling in non-prostatic malignancies: challenges and opportunities.Nature reviews. Cancer · 2025Review
- Oncolytic adenoviruses in bladder and kidney cancers: emerging strategies and next frontiers.Frontiers in microbiology · 2025Review
- Prognostic Significance of CCDC8 in Bladder Cancer: Insights from Bioinformatics and Immunohistochemical Analysis.Journal of Cancer · 2025Article
- Inhibition of KDM4A restricts SQLE transcription and induces oxidative stress imbalance to suppress bladder cancer.Redox biology · 2024Article
Corrections and comments
- Commented on byUro-Science.2024
Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
Disruption of KDM6A, a histone lysine demethylase, is one of the most common somatic alternations in bladder cancer. Insights into how KDM6A mutations affect the epigenetic landscape to promote carcinogenesis could help reveal potential new treatment approaches. Here, we demonstrated that KDM6A loss triggers an epigenetic switch that disrupts urothelial differentiation and induces a neoplastic state characterized by increased cell proliferation. In bladder cancer cells with intact KDM6A, FOXA1 interacted with KDM6A to activate genes instructing urothelial differentiation. KDM6A-deficient cells displayed simultaneous loss of FOXA1 target binding and genome-wide redistribution of the bZIP transcription factor ATF3, which in turn repressed FOXA1-target genes and activated cell-cycle progression genes. Importantly, ATF3 depletion reversed the cell proliferation phenotype induced by KDM6A deficiency. These data establish that KDM6A loss engenders an epigenetic state that drives tumor growth in an ATF3-dependent manner, creating a potentially targetable molecular vulnerability. SIGNIFICANCE: A gain-of-function epigenetic switch that disrupts differentiation is triggered by inactivating KDM6A mutations in bladder cancer and can serve as a potential target for novel therapies.
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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.