The role of the SWI/SNF chromatin remodeling complex in pancreatic ductal adenocarcinoma

• Published in: Cancer science Vol. 112; no. 2; pp. 490 - 497
• Main Authors: Tsuda, Motoyuki, Fukuda, Akihisa, Kawai, Munenori, Araki, Osamu, Seno, Hiroshi
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-02-2021; John Wiley and Sons Inc
• Subjects: Adenocarcinoma; Animals; BAF; Cancer; Carcinogenesis; Carcinogenesis - genetics; Carcinoma, Pancreatic Ductal - genetics; Cell cycle; Chromatin Assembly and Disassembly - genetics; Chromatin remodeling; chromatin remodeling complexes; Chromosomal Proteins, Non-Histone - genetics; Epigenetics; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Genomes; Humans; Kinases; Leukemia; Metabolism; Mutation; Nucleosomes; Pancreas; pancreatic ductal adenocarcinoma; Pancreatic Neoplasms; Pancreatic Neoplasms - genetics; Review; Roles; Sarcoma; SWI/SNF; SWI/SNF complex; Therapeutic applications; Therapeutic targets; Transcription factors; Transcription Factors - genetics; Tumorigenesis; chromatin remodeling complexes; epigenetics; BAF; SWI/SNF; pancreatic ductal adenocarcinoma
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.14768

ATP‐dependent chromatin remodeling complexes are a group of epigenetic regulators that can alter the assembly of nucleosomes and regulate the accessibility of transcription factors to DNA in order to modulate gene expression. One of these complexes, the SWI/SNF chromatin remodeling complex is mutated in more than 20% of human cancers. We have investigated the roles of the SWI/SNF complex in pancreatic ductal adenocarcinoma (PDA), which is the most lethal type of cancer. Here, we reviewed the recent literature regarding the role of the SWI/SNF complex in pancreatic tumorigenesis and current knowledge about therapeutic strategies targeting the SWI/SNF complex in PDA. The subunits of the SWI/SNF complex are mutated in 14% of human PDA. Recent studies have shown that they have context‐dependent oncogenic or tumor‐suppressive roles in pancreatic carcinogenesis. To target its tumor‐suppressive properties, synthetic lethal strategies have recently been developed. In addition, their oncogenic properties could be novel therapeutic targets. The SWI/SNF subunits are potential therapeutic targets for PDA, and further understanding of the precise role of the SWI/SNF complex subunits in PDA is required for further development of novel strategies targeting SWI/SNF subunits against PDA.
Here, we reviewed the recent literature regarding the role of the SWI/SNF complex in pancreatic tumorigenesis and current knowledge about therapeutic strategies targeting the SWI/SNF complex in pancreatic cancer. The SWI/SNF subunits are potential therapeutic targets for PDA, and further understanding of the precise role of the SWI/SNF complex subunits in PDA is required for further development of novel strategies targeting SWI/SNF subunits against PDA.