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Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2

ABSTRACT: Adenosquamous lung tumors may result from cellular plasticity. We demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, included Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions.

ORGANISM(S): Mus musculus

PROVIDER: GSE94365 | GEO | 2017/02/02

SECONDARY ACCESSION(S): PRJNA369478

REPOSITORIES: GEO

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