AI Article Synopsis
- - Prostate cancer (PCa) is common in men, and cancer stem cells are linked to its recurrence, with BAZ2A playing a key role in maintaining a cancer stem-like state in these cells.
- - BAZ2A binds to specific regions in the DNA marked by H3K14ac, which helps repress genes that are often silenced in aggressive PCa, indicating its importance in gene regulation.
- - Targeting BAZ2A and its interactions may offer new therapeutic strategies to combat aggressive forms of prostate cancer by disrupting the cancer stem cell characteristics.
Article Abstract
Prostate cancer (PCa) is one of the most prevalent cancers in men. Cancer stem cells are thought to be associated with PCa relapse. Here, we show that BAZ2A is required for PCa cells with a cancer stem-like state. BAZ2A genomic occupancy in PCa cells coincides with H3K14ac-enriched chromatin regions. This association is mediated by BAZ2A-bromodomain (BAZ2A-BRD) that specifically binds H3K14ac. BAZ2A associates with inactive enhancers marked by H3K14ac and repressing transcription of genes frequently silenced in aggressive and poorly differentiated PCa. BAZ2A-mediated repression is also linked to EP300 that acetylates H3K14ac. BAZ2A-BRD mutations or treatment with inhibitors abrogating BAZ2A-BRD/H3K14ac interaction impair PCa stem cells. Furthermore, pharmacological inactivation of BAZ2A-BRD impairs Pten-loss oncogenic transformation of prostate organoids. Our findings indicate a role of BAZ2A-BRD in PCa stem cell features and suggest potential epigenetic-reader therapeutic strategies to target BAZ2A in aggressive PCa.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567280 | PMC |
| http://dx.doi.org/10.15252/embr.202153014 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!