Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer

doi:10.1016/j.ccell.2020.05.019

	Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer
	Tang, Yang 1,2; Fang, Gemin 3,4; Guo, Fenghua 5; Zhang, Hui 1; Chen, Xiaoxu 3,4; An, Liwei 2; Chen, Min 2; Zhou, Li1,6 ; Wang, Wenjia 1; Ye, Tiantian 1; Zhou, Lei 7,8; Nie, Pingping 1; Yu, Haijun 7,8; Lin, Moubin 9; Zhao, Yun 1; Lin, Xinhua 10; Yuan, Zengqiang 11; Jiao, Shi 1; Zhou, Zhaocai 10
	2020-07-13
发表期刊	CANCER CELL (IF:48.8[JCR-2023],42.1[5-Year])
ISSN	1535-6108
EISSN	1878-3686
卷号	38 期号:1 页码:115-+
发表状态	已发表
DOI	10.1016/j.ccell.2020.05.019
摘要	Loss of Hippo tumor-suppressor activity and hyperactivation of YAP are commonly observed in cancers. Inactivating mutations of Hippo kinases MST1/2 are uncommon, and it remains unclear how their activity is turned off during tumorigenesis. We identified STRN3 as an essential regulatory subunit of protein phosphatase 2A (PP2A) that recruits MST1/2 and promotes its dephosphorylation, which results in YAP activation. We also identified STRN3 upregulation in gastric cancer correlated with YAP activation and poor prognosis. Based on this mechanistic understanding and aided by structure-guided medicinal chemistry, we developed a highly selective peptide inhibitor, STRN3-derived Hippo-activating peptide, or SHAP, which disrupts the STRN3-PP2Aa interaction and reactivates the Hippo tumor suppressor, inhibits YAP activation, and has antitumor effects in vivo.
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[81725014][81822035][81773212][21807001][31630047][31930026][81972876][81902806][81902389] ; National Key R&D Program of China[2017YFA0504504] ; Science and Technology Commission of Shanghai Municipality[19J1415600][19PJ1408300] ; Strategic Priority Research Program[XDB19020202][XDA12010315]
WOS研究方向	Oncology ; Cell Biology
WOS类目	Oncology ; Cell Biology
WOS记录号	WOS:000550244200016
出版者	CELL PRESS
WOS关键词	TISSUE HOMEOSTASIS ; TEAD/TEF FAMILY ; SIZE-CONTROL ; YAP ; PATHWAY ; MECHANISM ; INSIGHTS ; THERAPY
原始文献类型	Article
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/122688
专题	生命科学与技术学院_硕士生
通讯作者	Jiao, Shi; Zhou, Zhaocai
作者单位	1.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci,State Key Lab Cel, Shanghai 200031, Peoples R China 2.Tongji Univ, Shanghai Peoples Hosp 10, Dept Med Ultrasound,Sch Med, Canc Ctr,Postdoctoral Stn Clin Med,Ultrasound Res, Shanghai 200072, Peoples R China 3.Anhui Univ, Inst Phys Sci, Hefei 230601, Peoples R China 4.Anhui Univ, Inst Informat Technol, Hefei 230601, Peoples R China 5.Fudan Univ, Shanghai Med Coll, Huashan Hosp, Dept Gen Surg, Shanghai 200040, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 7.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 8.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China 9.Tongji Univ, Sch Med, Yangpu Hosp, Dept Gen Surg, Shanghai 200090, Peoples R China 10.Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200438, Peoples R China 11.Beijing Inst Basic Med Sci, Beijing 100850, Peoples R China
推荐引用方式 GB/T 7714	Tang, Yang,Fang, Gemin,Guo, Fenghua,et al. Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer[J]. CANCER CELL,2020,38(1):115-+.
APA	Tang, Yang.,Fang, Gemin.,Guo, Fenghua.,Zhang, Hui.,Chen, Xiaoxu.,...&Zhou, Zhaocai.(2020).Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer.CANCER CELL,38(1),115-+.
MLA	Tang, Yang,et al."Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer".CANCER CELL 38.1(2020):115-+.