YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression

	YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression
	Gao, YJ; Zhang, WJ; Han, XK; Li, FM; Wang, XJ; Wang, R; Fang, ZY; Tong, XY; Yao, S; Li, F
刊名	NATURE COMMUNICATIONS
	2014
卷号	5 期号:1 页码:4629-4629
通讯作者	Zhang, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.,RayZhang@sibcb.ac.cn
英文摘要	Whether the Hippo pathway contributes to cell lineage transition under pathological conditions, especially tumorigenesis, remains largely unknown. Here we show that YAP, the major effector of the Hippo pathway, displays a distinct activation pattern in lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC); YAP is initially activated by LKB1 loss in lung ADC, which upregulates ZEB2 expression and represses DNp63 transcription in a default manner. During transdifferentiation, YAP is inactivated, which in turn relieves ZEB2-mediated default repression of DNp63 and triggers squamous differentiation reprogramming. Disruption of the YAP barrier for phenotypic transition significantly accelerates squamous transdifferentiation, whereas constitutive YAP activation conversely inhibits this transition. More importantly, ectopic DNp63 expression rescues the inhibitory effect of YAP on squamous transdifferentiation. These findings have established YAP as an essential barrier for lung cancer cell fate conversion and provided a mechanism for regulating cancer plasticity, which might hold important implication for YAP-targeted therapies.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	YES-ASSOCIATED PROTEIN ; TUMOR-SUPPRESSOR PATHWAY ; STEM-LIKE CELLS ; HIPPO PATHWAY ; ADENOSQUAMOUS CARCINOMA ; HEPATOCELLULAR-CARCINOMA ; SIZE-CONTROL ; ORGAN SIZE ; CANCER ; DIFFERENTIATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000341057000020
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/284]
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	Gao, YJ,Zhang, WJ,Han, XK,et al. YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression[J]. NATURE COMMUNICATIONS,2014,5(1):4629-4629.
APA	Gao, YJ.,Zhang, WJ.,Han, XK.,Li, FM.,Wang, XJ.,...&Ji, HB.(2014).YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression.NATURE COMMUNICATIONS,5(1),4629-4629.
MLA	Gao, YJ,et al."YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression".NATURE COMMUNICATIONS 5.1(2014):4629-4629.