MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway

doi:10.1084/jem.20191817

	MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway
	An, Liwei 1; Nie, Pingping 2; Chen, Min 1; Tang, Yang 1; Zhang, Hui 2; Guan, Jingmin 2; Cao, Zhifa 2; Hou, Chun3 ; Wang, Wenjia 2; Zhao, Yun 2; Xu, Huixiong 1; Jiao, Shi 2; Zhou, Zhaocai2,3
	2020-06
发表期刊	JOURNAL OF EXPERIMENTAL MEDICINE
ISSN	0022-1007
EISSN	1540-9538
卷号	217 期号:6
发表状态	已发表
DOI	10.1084/jem.20191817
摘要	Hyperactivation of YAP has been commonly associated with tumorigenesis, and emerging evidence hints at multilayered Hippo-independent regulations of YAP. In this study, we identified a new MST4-YAP axis, which acts as a noncanonical Hippo signaling pathway that limits stress-induced YAP activation. MST4 kinase directly phosphorylated YAP at Thr83 to block its binding with importin a, therefore leading to YAP cytoplasmic retention and inactivation. Due to a consequential interplay between MST4-mediated YAP phospho-Thr83 signaling and the classical YAP phospho-Ser127 signaling, the phosphorylation level of YAP at Thr83 was correlated to that at Ser127. Mutation of T83E mimicking MST4-mediated alternative signaling restrained the activity of both wild-type YAP and its S127A mutant mimicking loss of classical Hippo signal. Depletion of MST4 in mice promoted gastric tumorigenesis with diminished Thr83 phosphorylation and hyperactivation of YAP. Moreover, loss of MST4-YAP signaling was associated with poor prognosis of human gastric cancer. Collectively, our study uncovered a noncanonical MST4-YAP signaling axis essential for suppressing gastric tumorigenesis.
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收录类别	SCI ; SCIE
语种	英语
资助项目	National Key R&D Program of China[2017YFA0504504] ; Shanghai Pujiang Program[19PJ1408300] ; National Natural Science Foundation of China[81902806][81725014][31930026][81822035][81773212][81972876][81902389][81802399][81927801][81725008] ; Strategic Priority Research Program[XDB19020202][XDA12010315] ; Fundamental Research Funds for the Central Universities[22120190021][22120190213][22120190137] ; Shanghai Municipal Health Commission[2019LJ21]
WOS研究方向	Immunology ; Research & Experimental Medicine
WOS类目	Immunology ; Medicine, Research & Experimental
WOS记录号	WOS:000538138000013
出版者	ROCKEFELLER UNIV PRESS
WOS关键词	HIPPO SIGNALING PATHWAY ; UPSTREAM SIGNALS ; TISSUE-GROWTH ; ORGAN SIZE ; PHOSPHORYLATION ; CANCER ; YAP/TAZ ; PROTEIN ; INACTIVATION ; METHYLATION
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/121674
专题	生命科学与技术学院_硕士生生命科学与技术学院_特聘教授组_周兆才组
通讯作者	Xu, Huixiong; Jiao, Shi; Zhou, Zhaocai
作者单位	1.Tongji Univ, Dept Med Ultrasound, Shanghai Peoples Hosp 10,Sch Med, Ultrasound Res & Educ Inst,Canc Ctr,Shanghai Engn, Shanghai, Peoples R China 2.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol,CAS Ctr Excellence Mol Ce, Shanghai, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	An, Liwei,Nie, Pingping,Chen, Min,et al. MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway[J]. JOURNAL OF EXPERIMENTAL MEDICINE,2020,217(6).
APA	An, Liwei.,Nie, Pingping.,Chen, Min.,Tang, Yang.,Zhang, Hui.,...&Zhou, Zhaocai.(2020).MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway.JOURNAL OF EXPERIMENTAL MEDICINE,217(6).
MLA	An, Liwei,et al."MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway".JOURNAL OF EXPERIMENTAL MEDICINE 217.6(2020).