| Title | Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity. |
| Publication Type | Journal Article |
| Year of Publication | 2020 |
| Authors | Cyrta J, Augspach A, De Filippo MRosaria, Prandi D, Thienger P, Benelli M, Cooley V, Bareja R, Wilkes D, Chae S-S, Cavaliere P, Dephoure N, Uldry A-C, Lagache SBraga, Roma L, Cohen S, Jaquet M, Brandt LP, Alshalalfa M, Puca L, Sboner A, Feng F, Wang S, Beltran H, Lotan T, Spahn M, de Julio MKruithof-, Chen Y, Ballman KV, Demichelis F, Piscuoglio S, Rubin MA |
| Journal | Nat Commun |
| Volume | 11 |
| Issue | 1 |
| Pagination | 5549 |
| Date Published | 2020 11 03 |
| ISSN | 2041-1723 |
| Keywords | Adenocarcinoma, Cell Line, Tumor, Cell Lineage, Cell Plasticity, Chromosomal Proteins, Non-Histone, Cohort Studies, DNA Helicases, Gene Expression Regulation, Neoplastic, Humans, Kaplan-Meier Estimate, Male, Models, Biological, Neoplasm Invasiveness, Neoplasm Proteins, Neuroendocrine Tumors, Nuclear Proteins, Prostatic Neoplasms, Protein Subunits, Transcription Factors, Transcriptome |
| 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. |
| DOI | 10.1038/s41467-020-19328-1 |
| Alternate Journal | Nat Commun |
| PubMed ID | 33144576 |
| PubMed Central ID | PMC7642293 |
| Grant List | R01 CA233650 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States R01 CA125612 / CA / NCI NIH HHS / United States R01 CA208100 / CA / NCI NIH HHS / United States R37 CA241486 / CA / NCI NIH HHS / United States P50 CA211024 / CA / NCI NIH HHS / United States U54 CA224079 / CA / NCI NIH HHS / United States U01 CA224044 / CA / NCI NIH HHS / United States |
Related Faculty:
Andrea Sboner, Ph.D.