Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models

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...

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Autores: Peinado, P. (Paola)|||/items/1dc3ecb0-434d-4544-83e4-211962d2f4ad, Andrades, A. (Alvaro)|||/items/e2b658b8-c400-4cab-9860-914b423a5d54, Cuadros, M. (Marta)|||/items/e8264bf7-3f94-4449-ad23-7baaba4fa9bc, Rodriguez-Lara, M.I. (Maria Isabel)|||/items/d4a12388-2ca2-473f-bc98-4c95baebea6d, Coira, I.F. (Isabel F.)|||/items/1948f876-fb8d-446f-a52a-36f7aab16d66, Garcia, D.J. (Daniel J.)|||/items/d73b79b5-31c7-4b3c-9176-d7fd81cd747d, Álvarez-Perez, J.C. (Juan Carlos)|||/items/03360ef7-e6fe-4791-b844-ddf2481b75ee, Baliñas-Gavira, C. (Carlos)|||/items/e32bc8ba-c624-468e-bc51-88dd94357fdc, Arenas, A.M. (Alberto M.)|||/items/4793dbe3-ff0a-4d0a-ba68-8414fdc6ce48, Patiño-Mercau, J.R. (Juan Rodrigo)|||/items/88987f7d-ffb1-4841-a829-3177239e1190, Sanjuan-Hidalgo, J. (Juan)|||/items/a8165a36-8176-4a2b-a863-f690e6ffd3a6, Romero, O.A. (Octavio A.)|||/items/946c1a42-0510-415f-9b6e-4ce94b463730, Montuenga-Badia, L.M. (Luis M.)|||/items/4c999705-b2c9-45ac-ba13-3f18594ae596, Carretero, J. (Julian)|||/items/c809e00c-b070-41aa-98a2-dfe39b3ff0f3, Sanchez-Cespedes, M. (Montserrat)|||/items/aaf33cf5-6f66-47a3-9c7b-f14e57d3cc88, Medina, P.P. (Pedro P.)|||/items/49f11e06-d63d-46b1-a642-bcff0f620dbd
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/65775
Acceso en línea:https://hdl.handle.net/10171/65775
Access Level:acceso abierto
Palabra clave:SWI/SNF complex
Lung cancer
Lung adenocarcinoma
Epigenetics
Cell models
Multi-omics
Descripción
Sumario: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.

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