Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer.

ABSTRACT: Lung cancer is a devastating disease that remains a top cause of cancer mortality. Despite improvements with targeted and immunotherapies, the majority of patients with lung cancer lack effective therapies, underscoring the need for additional treatment approaches. Genomic studies have identified frequent alterations in components of the SWI/SNF chromatin remodeling complex including SMARCA4 and ARID1A. To understand the mechanisms of tumorigenesis driven by mutations in this complex, we developed a genetically engineered mouse model of lung adenocarcinoma by ablating Smarca4 in the lung epithelium. We demonstrate that Smarca4 acts as a bona fide tumor suppressor and cooperates with p53 loss and Kras activation. Gene expression analyses revealed the signature of enhanced oxidative phosphor

SUBMITTER: Lissanu Deribe Y 

PROVIDER: S-EPMC6650267 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature