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

doi:10.1038/ncomms14922

	Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2
	Zhang, Haikuo 1,2; Brainson, Christine Fillmore 3,4,5,6,19; Koyama, Shohei 1,2; Redig, Amanda J.1,2; Chen, Ting 1,2; Li, Shuai 1,2; Gupta, Manav 3,4,6; Garcia-de-Alba, Carolina 3,4,5,6; Paschini, Margherita 3,4,5,6; Herter-Sprie, Grit S.1,2; Lu, Gang 1,2; Zhang, Xin 1,2; Marsh, Bryan P.3,4; Tuminello, Stephanie J.7; Xu, Chunxiao 1,2; Chen, Zhao 1,2; Wang, Xiaoen 1,2; Akbay, Esra A.1,2; Zheng, Mei 2; Palakurthi, Sangeetha 8; Sholl, Lynette M.1,2; Rustgi, Anil K.9; Kwiatkowski, David J.1,2; Diehl, J. Alan 10; Bass, Adam J.1,2; Sharpless, Norman E.11; Dranoff, Glenn 1,2; Hammerman, Peter S.1,2; Ji, Hongbin12,13 ; Bardeesy, Nabeel 14; Saur, Dieter 15,16,17; Watanabe, Hideo 8; Kim, Carla F.3,4,5,6; Wong, Kwok-Kin 1,2,8,18
	2017-04-07
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	8
发表状态	已发表
DOI	10.1038/ncomms14922
摘要	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, DNp63 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.
收录类别	SCI
语种	英语
资助项目	NIH/NCI[P01 CA120964] ; NIH/NCI[5R01CA163896-04] ; NIH/NCI[1R01CA195740-01] ; NIH/NCI[5R01CA140594-07] ; NIH/NCI[5R01CA122794-10] ; NIH/NCI[5R01CA166480-04]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000398455100001
出版者	NATURE PUBLISHING GROUP
WOS关键词	SQUAMOUS-CELL CARCINOMA ; BRONCHIOALVEOLAR STEM-CELLS ; MESENCHYMAL TRANSITION ; PROGENITOR CELLS ; MOUSE MODEL ; HISTONE H3 ; ADENOCARCINOMA ; EZH2 ; ORIGIN ; ALVEOLAR
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1420
专题	生命科学与技术学院_特聘教授组_季红斌组
通讯作者	Kim, Carla F.; Wong, Kwok-Kin
作者单位	1.Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA 2.Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Boston, MA 02115 USA 3.Boston Childrens Hosp Boston, Stem Cell Program, Boston, MA 02115 USA 4.Boston Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA 5.Harvard Med Sch, Dept Genet, Boston, MA 02115 USA 6.Harvard Stem Cell Inst, Cambridge, MA 02138 USA 7.Tisch Canc Inst, Icahn Sch Med Mt Sinai, Dept Med, Div Pulm Crit Care & Sleep Med, New York, NY 10029 USA 8.Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA 9.Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Dept Med & Genet,Div Gastroenterol, Philadelphia, PA 19104 USA 10.Univ South Carolina, Dept Biochem & Mol Biol Med, Charleston, SC 29425 USA 11.Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA 12.Chinese Acad Sci, Innovat Ctr Cell Signaling Network, Ctr Excellence Mol Cell Sci, Shanghai Inst Biol Sci,Inst Biochem & Cell Biol,K, Shanghai 200031, Peoples R China 13.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200120, Peoples R China 14.Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02144 USA 15.Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 2, D-81675 Munich, Germany 16.German Canc Res Ctr, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany 17.German Canc Consortium DKTK, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany 18.NYU, Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, New York, NY 10016 USA 19.Univ Kentucky, Dept Toxicol & Canc Biol, Lexington, KY 04536 USA
推荐引用方式 GB/T 7714	Zhang, Haikuo,Brainson, Christine Fillmore,Koyama, Shohei,et al. Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2[J]. NATURE COMMUNICATIONS,2017,8.
APA	Zhang, Haikuo.,Brainson, Christine Fillmore.,Koyama, Shohei.,Redig, Amanda J..,Chen, Ting.,...&Wong, Kwok-Kin.(2017).Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2.NATURE COMMUNICATIONS,8.
MLA	Zhang, Haikuo,et al."Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2".NATURE COMMUNICATIONS 8(2017).