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

Autor: Peinado P; Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, Spain.; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, 18016 Granada, Spain., Andrades A; Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, Spain.; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, 18016 Granada, Spain., Cuadros M; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, 18016 Granada, Spain.; Health Research Institute of Granada (ibs.Granada), 18014 Granada, Spain.; Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, 18016 Granada, Spain., Rodriguez MI; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, 18016 Granada, Spain.; Health Research Institute of Granada (ibs.Granada), 18014 Granada, Spain.; Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, 18016 Granada, Spain., Coira IF; School of Pharmaceutical Sciences, University of Geneva, 1211 Geneva, Switzerland.; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland., Garcia DJ; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, 18016 Granada, Spain.; Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, 18016 Granada, Spain., Álvarez-Perez JC; Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, Spain.; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, 18016 Granada, Spain., Baliñas-Gavira C; Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, Spain.; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, 18016 Granada, Spain., Arenas AM; Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, Spain.; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, 18016 Granada, Spain., Patiño-Mercau JR; Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, Spain.; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, 18016 Granada, Spain., Sanjuan-Hidalgo J; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, 18016 Granada, Spain., Romero OA; Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain., Montuenga LM; Solid Tumors Program, Centro de Investigación Médica Aplicada and Department of Pathology, Anatomy and Physiology, University of Navarra Pamplona, 31009 Pamplona, Spain.; Navarra's Health Research Institute (IDISNA) and CIBERONC, 31008 Pamplona, Spain., Carretero J; Department of Physiology, University of Valencia, 46100 Burjassot, Valencia, Spain., Sanchez-Cespedes M; Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain., Medina PP; Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, Spain.; GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, 18016 Granada, Spain.; Health Research Institute of Granada (ibs.Granada), 18014 Granada, Spain.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2020 Dec 10; Vol. 12 (12). Date of Electronic Publication: 2020 Dec 10.
DOI: 10.3390/cancers12123712
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje