Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity

Joanna Cyrta, Anke Augspach, Maria Rosaria Filippo, Davide Prandi, Phillip Thienger, Matteo Benelli, Victoria Cooley, Rohan Bareja, David Wilkes, Sung-Suk Chae, Paola Cavaliere, Noah Dephoure, Anne-Christine Uldry, Sophie Braga Lagache, Luca Roma, Sandra Cohen, Muriel Jaquet, Laura P. Brandt, Mohammed Alshalalfa, Loredana Puca, 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 and Mark A. Rubin ()
Additional contact information
Joanna Cyrta: University of Bern
Anke Augspach: University of Bern
Maria Rosaria Filippo: University of Bern
Davide Prandi: University of Trento
Phillip Thienger: University of Bern
Matteo Benelli: University of Trento
Victoria Cooley: Weill Cornell Medicine
Rohan Bareja: Weill Cornell Medicine
David Wilkes: Weill Cornell Medicine
Sung-Suk Chae: Weill Cornell Medicine
Paola Cavaliere: Weill Cornell Medicine
Noah Dephoure: Weill Cornell Medicine
Anne-Christine Uldry: University of Bern
Sophie Braga Lagache: University of Bern
Luca Roma: University Hospital Basel, University of Basel
Sandra Cohen: Weill Cornell Medicine
Muriel Jaquet: University of Bern
Laura P. Brandt: University of Bern
Mohammed Alshalalfa: University of California at San Francisco
Loredana Puca: Weill Cornell Medicine
Andrea Sboner: Weill Cornell Medicine
Felix Feng: University of Bern
Shangqian Wang: Memorial Sloan-Kettering Cancer Center
Himisha Beltran: Weill Cornell Medicine
Tamara Lotan: Johns Hopkins University School of Medicine
Martin Spahn: Prostate Center Bern
Marianna Kruithof- de Julio: University of Bern
Yu Chen: Weill Cornell Medicine
Karla V. Ballman: Weill Cornell Medicine
Francesca Demichelis: Weill Cornell Medicine
Salvatore Piscuoglio: University Hospital Basel, University of Basel
Mark A. Rubin: University of Bern

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19328-1

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DOI: 10.1038/s41467-020-19328-1

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