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.
Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity / Cyrta, J., Augspach, A., De Filippo, M.R., Prandi, D., Thienger, P., Benelli, M., Cooley, V., Bareja, R., Wilkes, D., Chae, S.-S., Cavaliere, P., Dephoure, N., Uldry, A.-C., Lagache, S.B., Roma, L., Cohen, S., Jaquet, M., Brandt, L.P., Alshalalfa, M., Puca, L., et al.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 11:1(2020), p. 5549. [10.1038/s41467-020-19328-1]
Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity
Prandi D.;Benelli M.;Sboner A.;Demichelis F.;
2020-01-01
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.| File | Dimensione | Formato | |
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