Two Hippo signaling modules orchestrate liver size and tumorigenesis

doi:10.15252/embj.2022112126

	Two Hippo signaling modules orchestrate liver size and tumorigenesis
	Qi, Sixian 1,2; Zhong, Zhenxing 1,2; Zhu, Yuwen 1,2; Wang, Yebin 1,2; Ma, Mingyue 1,2; Wang, Yu 1,2; Liu, Xincheng 1,2; Jin, Ruxin 1,2; Jiao, Zhihan 1,2; Zhu, Rui 1,2; Sha, Zhao 1,2; Dang, Kyvan 3; Liu, Ying 4; Lim, Dae-Sik 5; Mao, Junhao 3; Zhang, Lei6,7,8 ; Yu, Fa-Xing 1,2
	2023
发表期刊	EMBO JOURNAL; (IF:9.4[JCR-2023],11.0[5-Year])
ISSN	0261-4189
EISSN	1460-2075
发表状态	已发表
DOI	10.15252/embj.2022112126
摘要	The Hippo pathway is a central regulator of organ size and tumorigenesis and is commonly depicted as a kinase cascade, with an increasing number of regulatory and adaptor proteins linked to its regulation over recent years. Here, we propose that two Hippo signaling modules, MST1/2–SAV1–WWC1-3 (HPO1) and MAP4K1-7–NF2 (HPO2), together regulate the activity of LATS1/2 kinases and YAP/TAZ transcriptional co-activators. In mouse livers, the genetic inactivation of either HPO1 or HPO2 module results in partial activation of YAP/TAZ, bile duct hyperplasia, and hepatocellular carcinoma (HCC). On the contrary, inactivation of both HPO1 and HPO2 modules results in full activation of YAP/TAZ, rapid development of intrahepatic cholangiocarcinoma (iCCA), and early lethality. Interestingly, HPO1 has a predominant role in regulating organ size. HPO1 inactivation causes a homogenous YAP/TAZ activation and cell proliferation across the whole liver, resulting in a proportional and rapid increase in liver size. Thus, this study has reconstructed the order of the Hippo signaling network and suggests that LATS1/2 and YAP/TAZ activities are finetuned by HPO1 and HPO2 modules to cause different cell fates, organ size changes, and tumorigenesis trajectories.
关键词	Hippo liver cancer NF2 organ size YAP
学科门类	Neuroscience (all) ; Molecular Biology ; Biochemistry, Genetics and Molecular Biology (all) ; Immunology and Microbiology (all)
URL	查看原文
收录类别	SCOPUS ; SCI
语种	英语
资助项目	National Key R&D program of China["2020YFA0803202","2018YFA0800304","2019YFA0802001"] ; National Natural Science Foundation of China["81772965","32030025","32293233","32221002"] ; Science and Technology Commission of Shanghai Municipality["19JC1411100","21S11905000"] ; Shanghai Municipal Health Commission[2022XD049]
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000949240500001
出版者	WILEY
原始文献类型	Article
Scopus 记录号	2-s2.0-85149961336
来源库	SCOPUS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/286533
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_张雷组
通讯作者	Yu, Fa-Xing
作者单位	1.Fudan Univ, Childrens Hosp, Inst Pediat, Shanghai, Peoples R China 2.Fudan Univ, Inst Biomed Sci, Shanghai Med Coll,State Key Lab Genet Engn, Shanghai Key Lab Med Epigenet,Int Colab Med Epigen, Shanghai, Peoples R China 3.Univ Massachusetts, Dept Mol Cell & Canc Biol, Med Sch, Worcester, MA USA 4.Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Dept Pathol, Shanghai, Peoples R China 5.Korea Adv Inst Sci & Technol, Natl Creat Res Initiat Ctr, Dept Biol Sci, Daejeon, South Korea 6.Univ Chinese Acad Sci, Chinese Acad Sci, Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Shanghai, Peoples R China 7.Shanghai Jiao Tong Univ, Sheng Yushou Ctr Cell Biol & Immunol, Sch Life Sci & Biotechnol, Shanghai, Peoples R China 8.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Qi, Sixian,Zhong, Zhenxing,Zhu, Yuwen,et al. Two Hippo signaling modules orchestrate liver size and tumorigenesis[J]. EMBO JOURNAL;,2023.
APA	Qi, Sixian.,Zhong, Zhenxing.,Zhu, Yuwen.,Wang, Yebin.,Ma, Mingyue.,...&Yu, Fa-Xing.(2023).Two Hippo signaling modules orchestrate liver size and tumorigenesis.EMBO JOURNAL;.
MLA	Qi, Sixian,et al."Two Hippo signaling modules orchestrate liver size and tumorigenesis".EMBO JOURNAL; (2023).