ArticleOncogene2020
Hypermethylation of FOXA1 and allelic loss of PTEN drive squamous differentiation and promote heterogeneity in bladder cancer.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
- Mechanisms and implications of epithelial cell plasticity in the bladder.Nature reviews. Urology · 2026Review
- The Role of DNA Methyltransferases in Urinary System Diseases.Cancer innovation · 2025Review
- PTEN-mediated resistance in cancer: From foundation to future therapies.Toxicology reports · 2025Review
- PTEN loss drives p53 LOH and immune evasion in a novel urothelial organoid model harboring p53 missense mutations.Oncogene · 2025Article
- Interferon-γ/Janus Kinase 1/STAT1 Signaling Represses Forkhead Box A1 and Drives a Basal Transcriptional State in Muscle-Invasive Bladder Cancer.The American journal of pathology · 2025Article
- Epigenetic modifications in bladder cancer: crosstalk between DNA methylation and miRNAs.Frontiers in immunology · 2025Review
- FOXA1 and FOXA2: the regulatory mechanisms and therapeutic implications in cancer.Cell death discovery · 2024Review
- The urothelial gene regulatory network: understanding biology to improve bladder cancer management.Oncogene · 2024Review
- KDM6A Loss Triggers an Epigenetic Switch That Disrupts Urothelial Differentiation and Drives Cell Proliferation in Bladder Cancer.Cancer research · 2023Article
- FOXA1 repression drives lineage plasticity and immune heterogeneity in bladder cancers with squamous differentiation.Nature communications · 2022Article
- Chronic Arsenic Exposure Upregulates the Expression of Basal Transcriptional Factors and Increases Invasiveness of the Non-Muscle Invasive Papillary Bladder Cancer Line RT4.International journal of molecular sciences · 2022Article
- Sex differences in the aging murine urinary bladder and influence on the tumor immune microenvironment of a carcinogen-induced model of bladder cancer.Biology of sex differences · 2022Article
- Activation of PPARγ in bladder cancer via introduction of the long arm of human chromosome 9.Oncology letters · 2022Article
- Characterization of laminin-332 gene expression in molecular subtypes of human bladder cancer.American journal of clinical and experimental urology · 2022Article
- Alterations of Chromatin Regulators in the Pathogenesis of Urinary Bladder Urothelial Carcinoma.Cancers · 2021Review
- Review
- Subtype-associated epigenomic landscape and 3D genome structure in bladder cancer.Genome biology · 2021Article
- Novel Tyrosine Kinase Targets in Urothelial Carcinoma.International journal of molecular sciences · 2021Review
- DNA Methylation Modification Map to Predict Tumor Molecular Subtypes and Efficacy of Immunotherapy in Bladder Cancer.Frontiers in cell and developmental biology · 2021Article
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18 authors at 5 institutions in 1 country.
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Abstract
Intratumoral heterogeneity in bladder cancer is a barrier to accurate molecular sub-classification and treatment efficacy. However, individual cellular and mechanistic contributions to tumor heterogeneity are controversial. We examined potential mechanisms of FOXA1 and PTEN inactivation in bladder cancer and their contribution to tumor heterogeneity. These analyses were complemented with inactivation of FOXA1 and PTEN in intermediate and luminal mouse urothelium. We show inactivation and reduced expression of FOXA1 and PTEN is prevalent in human disease, where PTEN and FOXA1 are downregulated by allelic loss and site-specific DNA hypermethylation, respectively. Conditional inactivation of both Foxa1 and Pten in intermediate/luminal cells in mice results in development of bladder cancer exhibiting squamous features as well as enhanced sensitivity to a bladder-specific carcinogen. In addition, FOXA1 is hypermethylated in basal bladder cancer cell lines, and this is reversed by treatment with DNA methyltransferase inhibitors. By integrating human correlative and in vivo studies, we define a critical role for PTEN loss and epigenetic silencing of FOXA1 in heterogeneous human disease and show genetic targeting of luminal/intermediate cells in mice drives squamous differentiation.
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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.