Epigenetic basis of oncogenic-Kras-mediated epithelial-cellular proliferation and plasticity.

ABSTRACT: Oncogenic Kras induces a hyper-proliferative state that permits cells to progress to neoplasms in diverse epithelial tissues. Depending on the cell of origin, this also involves lineage transformation. Although a multitude of downstream factors have been implicated in these processes, the precise chronology of molecular events controlling them remains elusive. Using mouse models, primary human tissues, and cell lines, we show that, in Kras-mutant alveolar type II cells (AEC2), FOSL1-based AP-1 factor guides the mSWI/SNF complex to increase chromatin accessibility at genomic loci controlling the expression of genes necessary for neoplastic transformation. We identified two orthogonal processes in Kras-mutant distal airway club cells. The first promoted their transdifferentiation into an AEC

SUBMITTER: Kadur Lakshminarasimha Murthy P 

PROVIDER: S-EPMC8938988 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature