Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models
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AuteurPeinado, Paola; Andrades Delgado, Álvaro; Cuadros Celorrio, Marta Eugenia; Rodríguez Lara, María Isabel; García García, Daniel Jesús; Álvarez Pérez, Juan Carlos; Baliñas Gavira, Carlos; Arenas Molina, Alberto Manuel; Patiño Mercau, Juan Rodrigo; Sanjuan Hidalgo, Juan; Medina Vico, Pedro Pablo
SWI/SNF complexLung cancerLung adenocarcinomaEpigeneticsCell modelMulti-omics
Peinado, P., Andrades, A., Cuadros, M., Rodriguez, M. I., Coira, I. F., Garcia, D. J., ... & Medina, P. P. (2020). Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models. Cancers, 12(12), 3712. [doi:10.3390/cancers12123712]
PatrocinadorMinistry of Economy of Spain SAF2015-67919-R; Junta de Andalucía CS2016-3 P12-BIO1655 PIGE-0440-2019 Pl-0245-2017 PI-0135-2020; University of Granada PPJIA2019-0 B-CTS-126-UGR18; International Association for the Study of Lung Cancer (IASLC); Spanish Association for Cancer Research (LAB-AECC); PhD "La Caixa Foundation" LCF/BQ/DE15/10360019; "Fundacion Benefica Anticancer Santa Candida y San Francisco Javier" predoctoral fellowship; European Commission 837897; Spanish Ministry of Education, Culture and Sports FPU fellowship FPU17/00067 FPU17/01258 FPU18/03709; PhD FPI-fellowship BES-2013-064596; Fundación Científica de la Asociación Española Contra el Cáncer GCB14-2170; Fundación Ramon Areces; Instituto de Salud Carlos III-Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional `Una manera de hacer Europa' (FEDER) PI19/00098
Simple Summary: Mammalian SWI/SNF complexes regulate gene expression by reorganizing the way DNA is packaged into chromatin. SWI/SNF subunits are recurrently altered in tumors at multiple levels, including DNA mutations as well as alteration of the levels of RNA and protein. Cancer cell lines are often used to study SWI/SNF function, but their patterns of SWI/SNF alterations can be complex. Here, we present a comprehensive characterization of DNA mutations and RNA and protein expression of SWI/SNF members in 38 lung adenocarcinoma (LUAD) cell lines. We show that over 85% of our cell lines harbored at least one alteration in one SWI/SNF subunit. In addition, over 75% of our cell lines lacked expression of at least one SWI/SNF subunit at the protein level. Our catalog will help researchers choose an appropriate cell line model to study SWI/SNF function in LUAD. Abstract: 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 di erent SWI/SNF subunits. These results underline the importance of the SWI/SNF complex as a tumor suppressor in LUAD and the di culties 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.