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

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...

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Detalles Bibliográficos
Autores principales: Cyrta, Joanna, Augspach, Anke, De Filippo, Maria Rosaria, Prandi, Davide, Thienger, Phillip, Benelli, Matteo, Cooley, Victoria, Bareja, Rohan, Wilkes, David, Chae, Sung-Suk, Cavaliere, Paola, Dephoure, Noah, Uldry, Anne-Christine, Lagache, Sophie Braga, Roma, Luca, Cohen, Sandra, Jaquet, Muriel, Brandt, Laura P., Alshalalfa, Mohammed, Puca, Loredana, Sboner, Andrea, Feng, Felix, Wang, Shangqian, Beltran, Himisha, Lotan, Tamara, Spahn, Martin, Kruithof-de Julio, Marianna, Chen, Yu, Ballman, Karla V., Demichelis, Francesca, Piscuoglio, Salvatore, Rubin, Mark A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642293/
https://www.ncbi.nlm.nih.gov/pubmed/33144576
http://dx.doi.org/10.1038/s41467-020-19328-1
Descripción
Sumario: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.

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