Smarca4 Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung.

ABSTRACT: SMARCA4/BRG1 encodes for one of two mutually exclusive ATPases present in mammalian SWI/SNF chromatin remodeling complexes and is frequently mutated in human lung adenocarcinoma. However, the functional consequences of SMARCA4 mutation on tumor initiation, progression, and chromatin regulation in lung cancer remain poorly understood. Here, we demonstrate that loss of Smarca4 sensitizes club cell secretory protein-positive cells within the lung in a cell type-dependent fashion to malignant transformation and tumor progression, resulting in highly advanced dedifferentiated tumors and increased metastatic incidence. Consistent with these phenotypes, Smarca4-deficient primary tumors lack lung lineage transcription factor activities and resemble a metastatic c

SUBMITTER: Concepcion CP 

PROVIDER: S-EPMC8831463 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature