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.; Sboner, A.; Feng, F.; Wang, S.; Beltran, H.; Lotan, T.; Spahn, M.; Kruithof-de Julio, M.; Chen, Y.; Ballman, K. V.; Demichelis, F.; Piscuoglio, S.; Rubin, M. A.

doi:10.1038/s41467-020-19328-1

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.; Sboner A.; Feng F.; Wang S.; Beltran H.; Lotan T.; Spahn M.; Kruithof-de Julio M.; Chen Y.; Ballman K.V.; Demichelis F.; Piscuoglio S.; Rubin M.A.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - ELETTRONICO. - 11:(2020), pp. 5549.0-5549.0. [10.1038/s41467-020-19328-1]