ArticleInternational journal of cancer2020
Epigenetic plasticity potentiates a rapid cyclical shift to and from an aggressive cancer phenotype.
Article in International journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Recent advances in bladder cancer stem cells (BCSCs): A descriptive review of emerging therapeutic targets.iScience · 2025Review
- White-opaque switching inMicrobiology and molecular biology reviews : MMBR · 2024Review
- A novel DNA methylation signature revealed GDF6 and RCC1 as potential prognostic biomarkers correlated with cell proliferation in clear cell renal cell carcinoma.Molecular biology reports · 2023Article
- DNMT and EZH2 inhibitors synergize to activate therapeutic targets in hepatocellular carcinoma.Cancer letters · 2022Article
- Bladder cancer cells shift rapidly and spontaneously to cisplatin-resistant oxidative phosphorylation that is trackable in real time.Scientific reports · 2022Article
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- Role of themBio · 2021Article
- Characterizing DNA methylation signatures and their potential functional roles in Merkel cell carcinoma.Genome medicine · 2021Article
- Article
- A Novel DNA Methylation Signature as an Independent Prognostic Factor in Muscle-Invasive Bladder Cancer.Frontiers in oncology · 2021Article
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Highly tumorigenic, drug-resistant cancer stem-like cells drive cancer progression. These aggressive cells can arise repeatedly from bulk tumor cells independently of mutational events, suggesting an epigenetic mechanism. To test this possibility, we studied bladder cancer cells as they cyclically shifted to and from a cancer stem-like phenotype, and we discovered that these two states exhibit distinct DNA methylation and chromatin accessibility. Most differential chromatin accessibility was independent of methylation and affected the expression of driver genes such as E2F3, a cell cycle regulator associated with aggressive bladder cancer. Cancer stem-like cells exhibited increased E2F3 promoter accessibility and increased E2F3 expression that drove cell migration, invasiveness and drug resistance. Epigenetic interference using a DNA methylation inhibitor blocked the transition to a cancer stem-like state and reduced E2F3 expression. Our findings indicate that epigenetic plasticity plays a key role in the transition to and from an aggressive, drug-resistant phenotype.
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Registered trials
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