TY - JOUR T1 - Role of Specialized Composition of SWI/SNF Complexes in Prostate Cancer Lineage Plasticity JF - bioRxiv DO - 10.1101/2020.03.06.949131 SP - 2020.03.06.949131 AU - Joanna Cyrta AU - Anke Augspach AU - Maria Rosaria de Filippo AU - Davide Prandi AU - Phillip Thienger AU - Matteo Benelli AU - Victoria Cooley AU - Rohan Bareja AU - David Wilkes AU - Sung-Suk Chae AU - Paola Cavaliere AU - Noah Dephoure AU - Anne-Christine Uldry AU - Sophie Braga Lagache AU - Sandra Cohen AU - Muriel Jaquet AU - Laura P. Brandt AU - Mohammed Alshalalfa AU - Andrea Sboner AU - Felix Feng AU - Shangqian Wang AU - Himisha Beltran AU - Tamara Lotan AU - Martin Spahn AU - Marianna Kruithof-de Julio AU - Yu Chen AU - Karla V. Ballman AU - Francesca Demichelis AU - Salvatore Piscuoglio AU - Mark A. Rubin Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/03/08/2020.03.06.949131.abstract N2 - 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. ER -