커뮤니티

Global Group

Best your Partner

연구소세미나

게시글 검색
Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2.
종양연구소 조회수:374
2017-08-25 14:08:03

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

 

2017 Apr 7;8:14922. doi: 10.1038/ncomms14922.

 

Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, 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, including 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. The pattern of high EZH2, but low H3K27me3 mark, is also prevalent in human lung SCC and SCC regions within ADSCC tumours. Using FACS-isolated populations, we demonstrate that bronchioalveolar stem cells and club cells are the likely cells-of-origin for SCC transitioned tumours. These findings shed light on the epigenetics and cellular origins of lineage-specific lung tumours.

SNS 공유