Role of Specialized mSWI/SNF Complexes in Prostate Cancer Lineage Plasticity

Joanna Cyrta, et al.

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Received Date: 8th February 20

Joanna Cyrta, Anke Augspach, Maria Rosaria de Filippo, Davide Prandi, Philip Thienger, Matteo Benelli, Victoria Cooley, Rohan Bareja, David Wilkes, Sung-Suk Chae, Paola Cavaliere, Noah Dephoure, Anne-Christine Uldry, Sophie Braga Lagache, Sandra Cohen, Muriel Jaquet, Laura P. Brandt, Mohammed Alshalalfa, Andrea Sboner, Felix Feng, Shangqian Wang, Himisha Beltran, Tamara Lotan, Martin Spahn, Marianna Kruithof-de Julio, Yu Chen, Karla V. Ballman, Francesca Demichelis, Salvatore Piscuoglio,  Mark Rubin

Advanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in ~10% of these patients is through 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 suggest a role for mSWI/SNF complexes in therapy-related lineage plasticity, which may be relevant for other solid tumors. 

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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