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

文献类型：期刊论文

作者Tang, Yang2,3; Fang, Gemin4,5; Guo, Fenghua6; Zhang, Hui2; Chen, Xiaoxu4,5; An, Liwei3; Chen, Min3; Zhou, Li2,7; Wang, Wenjia2; Ye, Tiantian2
刊名CANCER CELL
出版日期2020-07-13
卷号38期号:1页码:115-+
ISSN号1535-6108
DOI10.1016/j.ccell.2020.05.019
通讯作者Jiao, Shi(jiaoshi@sibcb.ac.cn) ; Zhou, Zhaocai(zczhou@sibcb.ac.cn)
英文摘要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.
WOS关键词TISSUE HOMEOSTASIS ; TEAD/TEF FAMILY ; SIZE-CONTROL ; YAP ; PATHWAY ; MECHANISM ; INSIGHTS ; THERAPY
资助项目National Natural Science Foundation of China[81725014] ; National Natural Science Foundation of China[81822035] ; National Natural Science Foundation of China[81773212] ; National Natural Science Foundation of China[21807001] ; National Natural Science Foundation of China[31630047] ; National Natural Science Foundation of China[31930026] ; National Natural Science Foundation of China[81972876] ; National Natural Science Foundation of China[81902806] ; National Natural Science Foundation of China[81902389] ; National Key R&D Program of China[2017YFA0504504] ; Science and Technology Commission of Shanghai Municipality[19J1415600] ; Science and Technology Commission of Shanghai Municipality[19PJ1408300] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences ; Strategic Priority Research Program[XDB19020202] ; Strategic Priority Research Program[XDA12010315]
WOS研究方向Oncology ; Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:000550244200016
源URL[http://119.78.100.183/handle/2S10ELR8/292111]  
专题新药研究国家重点实验室
通讯作者Jiao, Shi; Zhou, Zhaocai
作者单位1.Beijing Inst Basic Med Sci, Beijing 100850, Peoples R China
2.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
3.Tongji Univ, Shanghai Peoples Hosp 10, Dept Med Ultrasound,Sch Med, Canc Ctr,Postdoctoral Stn Clin Med,Ultrasound Res, Shanghai 200072, Peoples R China
4.Anhui Univ, Inst Phys Sci, Hefei 230601, Peoples R China
5.Anhui Univ, Inst Informat Technol, Hefei 230601, Peoples R China
6.Fudan Univ, Shanghai Med Coll, Huashan Hosp, Dept Gen Surg, Shanghai 200040, Peoples R China
7.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
8.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
9.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
10.Tongji Univ, Sch Med, Yangpu Hosp, Dept Gen Surg, Shanghai 200090, 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-+.

入库方式： OAI收割

来源：上海药物研究所

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