Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33144576.
- Also identified by DOI 10.1038/s41467-020-19328-1 and PMC identifier 7642293.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Advanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in around 10-20% of these patients is lineage plasticity, which manifests in a partial or complete small cell or neuroendocrine prostate cancer (NEPC) phenotype. Here, we investigate the role of the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex in NEPC. Using large patient datasets, patient-derived organoids and cancer cell lines, we identify mSWI/SNF subunits that are deregulated in NEPC and demonstrate that SMARCA4 (BRG1) overexpression is associated with aggressive disease. We also show that SWI/SNF complexes interact with different lineage-specific factors in NEPC compared to prostate adenocarcinoma. These data point to a role for mSWI/SNF complexes in therapy-related lineage plasticity, which may also be relevant for other solid tumors.
Medical subject headings
- Cell Lineage
- Cell Plasticity
- Chromosomal Proteins, Non-Histone
- Prostatic Neoplasms
- Transcription Factors