Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity.
Adenocarcinoma
/ genetics
Cell Line, Tumor
Cell Lineage
Cell Plasticity
Chromosomal Proteins, Non-Histone
/ metabolism
Cohort Studies
DNA Helicases
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Kaplan-Meier Estimate
Male
Models, Biological
Neoplasm Invasiveness
Neoplasm Proteins
/ metabolism
Neuroendocrine Tumors
/ metabolism
Nuclear Proteins
/ genetics
Prostatic Neoplasms
/ genetics
Protein Subunits
/ metabolism
Transcription Factors
/ genetics
Transcriptome
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 11 2020
03 11 2020
Historique:
received:
08
02
2020
accepted:
07
10
2020
entrez:
4
11
2020
pubmed:
5
11
2020
medline:
25
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33144576
doi: 10.1038/s41467-020-19328-1
pii: 10.1038/s41467-020-19328-1
pmc: PMC7642293
doi:
Substances chimiques
Chromosomal Proteins, Non-Histone
0
Neoplasm Proteins
0
Nuclear Proteins
0
Protein Subunits
0
SWI-SNF-B chromatin-remodeling complex
0
Transcription Factors
0
SMARCA4 protein, human
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5549Subventions
Organisme : NCI NIH HHS
ID : R01 CA233650
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA125612
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA208100
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA241486
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA211024
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224079
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA224044
Pays : United States
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