Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma

	Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma
	Han, XK; Li, FM; Fang, ZY; Gao, YJ; Li, F; Fang, R; Yao, S; Sun, YH; Li, L; Zhang, WJ
刊名	NATURE COMMUNICATIONS
	2014
卷号	5 期号:1 页码:3261-3261
通讯作者	Ji, HB (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.,hbji@sibcb.ac.cn
英文摘要	Lineage transition in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of non-small cell lung cancer, as implicated by clinical observation of mixed ADC and SCC pathologies in adenosquamous cell carcinoma, remains a fundamental yet unsolved question. Here we provide in vivo evidence showing the transdifferentiation of lung cancer from ADC to SCC in mice: Lkb1-deficient lung ADC progressively transdifferentiates into SCC, via a pathologically mixed mAd-SCC intermediate. We find that reduction of lysyl oxidase (Lox) in Lkb1-deficient lung ADC decreases collagen disposition and triggers extracellular matrix remodelling and upregulates p63 expression, a SCC lineage survival oncogene. Pharmacological Lox inhibition promotes the transdifferentiation, whereas ectopic Lox expression significantly inhibits this process. Notably, ADC and SCC show differential responses to Lox inhibition. Collectively, our findings demonstrate the de novo transdifferentiation of lung ADC to SCC in mice and provide mechanistic insight that may have important implications for lung cancer treatment.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	PEUTZ-JEGHERS-SYNDROME ; HEMATOPOIETIC STEM-CELLS ; GROWTH-FACTOR RECEPTOR ; LYSYL OXIDASE ; TRANSGENIC MICE ; IN-VIVO ; K-RAS ; BETA-AMINOPROPIONITRILE ; ADENOSQUAMOUS CARCINOMA ; SOMATIC MUTATIONS
收录类别	SCI
语种	英语
WOS记录号	WOS:000332667600008
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/283]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Han, XK,Li, FM,Fang, ZY,et al. Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma[J]. NATURE COMMUNICATIONS,2014,5(1):3261-3261.
APA	Han, XK.,Li, FM.,Fang, ZY.,Gao, YJ.,Li, F.,...&Ji, HB.(2014).Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma.NATURE COMMUNICATIONS,5(1),3261-3261.
MLA	Han, XK,et al."Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma".NATURE COMMUNICATIONS 5.1(2014):3261-3261.