ArticleCell death & disease2017
Decitabine, a DNA-demethylating agent, promotes differentiation via NOTCH1 signaling and alters immune-related pathways in muscle-invasive bladder cancer.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Mechanisms and implications of epithelial cell plasticity in the bladder.Nature reviews. Urology · 2026Review
- Epigenetic editing of marine medaka (Zoological research · 2026Article
- The Role of DNA Methyltransferases in Urinary System Diseases.Cancer innovation · 2025Review
- DNA Methylation in Bladder Cancer: Diagnostic and Therapeutic Perspectives-A Narrative Review.International journal of molecular sciences · 2025Review
- Decitabine promotes the differentiation of poorly differentiated gastric cancer cells and enhances the sensitivity of NK cell cytotoxicity via TNF-α.Scientific reports · 2025Article
- The power and the promise of epigenetic drugs in oncology.Frontiers in genetics · 2025Review
- The role of DNA methylation and demethylation in bladder cancer: a focus on therapeutic strategies.Frontiers in oncology · 2025Review
- Emerging applications of hypomethylating agents in the treatment of glioblastoma (Review).Molecular and clinical oncology · 2024Review
- CTLA4 DNA methylation is associated with CTLA-4 expression and predicts response to immunotherapy in head and neck squamous cell carcinoma.Clinical epigenetics · 2023Article
- The Pyroptotic and Nonpyroptotic Roles of Gasdermins in Modulating Cancer Progression and Their Perspectives on Cancer Therapeutics.Archivum immunologiae et therapiae experimentalis · 2023Review
- Decitabine Treatment Induces a Viral Mimicry Response in Cervical Cancer Cells and Further Sensitizes Cells to Chemotherapy.International journal of molecular sciences · 2022Article
- DNA methylation signature predicts cancer response to demethylation agents from profiling diverse cancer cell lines.Cancer communications (London, England) · 2022Article
- Recurrent transcriptional responses in AML and MDS patients treated with decitabine.Experimental hematology · 2022Article
- Role of Chromatin Modifying Complexes and Therapeutic Opportunities in Bladder Cancer.Bladder cancer (Amsterdam, Netherlands) · 2022Review
- Zebularine elevates STING expression and enhances cGAMP cancer immunotherapy in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Tackling tumor microenvironment through epigenetic tools to improve cancer immunotherapy.Clinical epigenetics · 2021Review
- Targeting Germ Cell Tumors with the Newly Synthesized Flavanone-Derived Compound MLo1302 Efficiently Reduces Tumor Cell Viability and Induces Apoptosis and Cell Cycle Arrest.Pharmaceutics · 2021Article
- The Role of the Microenvironment in Controlling the Fate of Bioprinted Stem Cells.Chemical reviews · 2020Review
- Review
- Targeting the Immune system and Epigenetic Landscape of Urological Tumors.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
Aberrant DNA methylation observed in cancer can provide survival benefits to cells by silencing genes essential for anti-tumor activity. DNA-demethylating agents such as Decitabine (DAC)/Azacitidine (AZA) activate otherwise silenced tumor suppressor genes, alter immune response and epigenetically reprogram tumor cells. In this study, we show that non-cytotoxic nanomolar DAC concentrations modify the bladder cancer transcriptome to activate NOTCH1 at the mRNA and protein level, increase double-stranded RNA sensors and CK5-dependent differentiation. Importantly, DAC treatment increases ICN1 expression (the active intracellular domain of NOTCH1) significantly inhibiting cell proliferation and causing changes in cell size inducing morphological alterations reminiscent of senescence. These changes were not associated with β-galactosidase activity or increased p16 levels, but instead were associated with substantial IL-6 release. Increased IL-6 release was observed in both DAC-treated and ICN1 overexpressing cells as compared to control cells. Exogenous IL-6 expression was associated with a similar enlarged cell morphology that was rescued by the addition of a monoclonal antibody against IL-6. Treatment with DAC, overexpression with ICN1 or addition of exogenous IL-6 showed CK5 reduction, a surrogate marker of differentiation. Overall this study suggests that in MIBC cells, DNA hypomethylation increases NOTCH1 expression and IL-6 release to induce CK5-related differentiation.
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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.