Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models
Paola Peinado, Alvaro Andrades, Marta Cuadros, Maria Isabel Rodriguez, Isabel F Coira, Daniel J Garcia, Juan Carlos Álvarez-Perez, Carlos Baliñas-Gavira, Alberto M Arenas, Juan Rodrigo Patiño-Mercau, Juan Sanjuan-Hidalgo, Octavio A Romero, Luis M Montuenga, Julian Carretero, Montserrat Sanchez-Cespedes, Pedro P Medina
Mammalian SWI/SNF (SWitch/Sucrose Non-Fermentable) complexes are ATP-dependent chromatin remodelers whose subunits have emerged among the most frequently mutated genes in cancer. Studying SWI/SNF function in cancer cell line models has unveiled vulnerabilities in SWI/SNF-mutant tumors that can lead to the discovery of new therapeutic drugs.
However, choosing an appropriate cancer cell line model for SWI/SNF functional studies can be challenging because SWI/SNF subunits are frequently altered in cancer by various mechanisms, including genetic alterations and post-transcriptional mechanisms. In this work, we combined genomic, transcriptomic, and proteomic approaches to study the mutational status and the expression levels of the SWI/SNF subunits in a panel of 38 lung adenocarcinoma (LUAD) cell lines.
We found that the SWI/SNF complex was mutated in more than 76% of our LUAD cell lines and there was a high variability in the expression of the different SWI/SNF subunits. These results underline the importance of the SWI/SNF complex as a tumor suppressor in LUAD and the difficulties in defining altered and unaltered cell models for the SWI/SNF complex. These findings will assist researchers in choosing the most suitable cellular models for their studies of SWI/SNF to bring all of its potential to the development of novel therapeutic applications.
CITATION Cancers (Basel). 2020 Dec 10;12(12):3712. doi: 10.3390/cancers12123712.