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Updated: Dec 2, 2025

Evaluating the Differentiation Capacity of Mouse Prostate Epithelial Cells Using Organoid Culture
Published on: November 22, 2019
Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity
Joanna Cyrta1,2, Anke Augspach1, Maria Rosaria De Filippo3,4
1Department for BioMedical Research, University of Bern, 3008, Bern, Switzerland.
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.
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