Paper

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

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

2020

Overview

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.

• Publisher: Cold Spring Harbor Laboratory Press
• Subject: Adenocarcinoma / BRG1 protein / Chromatin remodeling / Organoids / Phenotypes / Plasticity / Prostate cancer / Solid tumors / Tumor cell lines