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 Detalle_Publicacion

ARID2 deficiency promotes tumor progression and is associated with higher sensitivity to chemotherapy in lung cancer

Abstract: The survival rate in lung cancer remains stubbornly low and there is an urgent need for the identification of new therapeutic targets. In the last decade, several members of the SWI/SNF chromatin remodeling complexes have been described altered in different tumor types. Nevertheless, the precise mechanisms of their impact on cancer progression, as well as the application of this knowledge to cancer patient management are largely unknown. In this study, we performed targeted sequencing of a cohort of lung cancer patients on genes involved in chromatin structure. In addition, we studied at the protein level the expression of these genes in cancer samples and performed functional experiments to identify the molecular mechanisms linking alterations of chromatin remodeling genes and tumor development. Remarkably, we found that 20% of lung cancer patients show ARID2 protein loss, partially explained by the presence of ARID2 mutations. In addition, we showed that ARID2 deficiency provokes profound chromatin structural changes altering cell transcriptional programs, which bolsters the proliferative and metastatic potential of the cells both in vitro and in vivo. Moreover, we demonstrated that ARID2 deficiency impairs DNA repair, enhancing the sensitivity of the cells to DNA-damaging agents. Our findings support that ARID2 is a bona fide tumor suppressor gene in lung cancer that may be exploited therapeutically.

 Autoría: Moreno T., Monterde B., González-Silva L., Betancor-Fernández I., Revilla C., Agraz-Doblas A., Freire J., Isidro P., Quevedo L., Blanco R., Montes-Moreno S., Cereceda L., Astudillo A., Casar B., Crespo P., Morales Torres C., Scaffidi P., Gómez-Román J., Salido E., Varela I.,

 Fuente: Oncogene 2021 Apr;40(16):2923-2935

Editorial: Basingstoke : Nature Publishing Group

 Año de publicación: 2021

Nº de páginas: 13

Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41388-021-01748-y

ISSN: 0950-9232,1476-5594

Proyecto español: SAF2012-31627 ; SAF2016-76758-R ; SAF-2015-63638R ; SAF-2015- 73364-JIN

Url de la publicación: https://www.doi.org/10.1038/s41388-021-01748-y

Autores/as

THAIDY MORENO RODRIGUEZ

LAURA GONZALEZ SILVA

BETANCOR-FERNÁNDEZ, ISABEL

CARLOS REVILLA GOMEZ

ANTONIO MANUEL AGRAZ DOBLAS

FREIRE, JAVIER

ISIDRO, PABLO

MONTES-MORENO, SANTIAGO

CERECEDA, LAURA

ASTUDILLO, AURORA

MORALES TORRES, CRISTINA

SCAFFIDI, PAOLA

GÓMEZ-ROMÁN, JAVIER

SALIDO, EDUARDO