KIB OpenIR
Cyclopeptide RA-V Inhibits Organ Enlargement and Tumorigenesis Induced by YAP Activation
Ji, Xinyan1,2; Song, Lihua3,4; Sheng, Li5; Gao, Anhui5; Zhao, Yang1,2; Han, Shixun1,2; Zhang, Yuchao1,2; Zhu, Chu1,2; Zhao, Simeng6; Wang, Zhe3,4; Xu, Bohan1,2; Li, Li7; Li, Jia5,8; Tan, Ninghua3,4,6; Zhao, Bin1,2
2018-11-01
Source PublicationCANCERS
ISSN2072-6694
Volume10Issue:11Pages:18
AbstractThe Hippo pathway restricts organ size during development and its inactivation plays a crucial role in cancer. Yes-associated protein (YAP) and its paralog transcriptional coactivator with PSD-95/Dlg/ZO-1 (PDZ)-binding motif (TAZ) are transcription co-activators and effectors of the Hippo pathway mediating aberrant enlargement of organs and tumor growth upon Hippo pathway inactivation. It has been demonstrated that genetic inactivation of YAP could be an effective approach to inhibit tumorigenesis. In order to identify pharmacological inhibitors of YAP, we screened a library of 52,683 compounds using a YAP-specific reporter assay. In this screen we identified cyclopeptide RA-V (deoxybouvardin) as a specific inhibitor of YAP and TAZ but not other reporters. Unexpectedly, later experiments demonstrated that RA-V represses the protein but not mRNA levels of YAP target genes. Nevertheless, RA-V strongly blocks liver enlargement induced by Mst1/2 knockout. Furthermore, RA-V not only inhibits liver tumorigenesis induced by YAP activation, but also induces regression of established tumors. We found that RA-V inhibits dedifferentiation and proliferation, while inducing apoptosis of hepatocytes. Furthermore, RA-V also induces apoptosis and inhibits proliferation of macrophages in the microenvironment, which are essential for YAP-induced tumorigenesis. RA-V is thus a drug candidate for cancers involving YAP/TAZ activation.
Keywordhippo pathway YAP TAZ RA-V cancer organ size protein synthesis
Indexed BySCI
Language英语
WOS IDWOS:000451307700056
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/63290
Collection中国科学院昆明植物研究所
Corresponding AuthorLi, Jia; Tan, Ninghua; Zhao, Bin
Affiliation1.Zhejiang Univ, Life Sci Inst, MOE Key Lab Biosyst Homeostasis & Protect, Hangzhou 310058, Zhejiang, Peoples R China
2.Zhejiang Univ, Life Sci Inst, Innovat Ctr Cell Signaling Network, Hangzhou 310058, Zhejiang, Peoples R China
3.China Pharmaceut Univ, Sch Tradit Chinese Pharm, Nanjing 211198, Jiangsu, Peoples R China
4.China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 211198, Jiangsu, Peoples R China
5.Natl Ctr Drug Screening, 189 Guoshoujing Rd, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
7.Hangzhou Normal Univ, Inst Aging Res, Hangzhou 311121, Zhejiang, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
Recommended Citation
GB/T 7714
Ji, Xinyan,Song, Lihua,Sheng, Li,et al. Cyclopeptide RA-V Inhibits Organ Enlargement and Tumorigenesis Induced by YAP Activation[J]. CANCERS,2018,10(11):18.
APA Ji, Xinyan.,Song, Lihua.,Sheng, Li.,Gao, Anhui.,Zhao, Yang.,...&Zhao, Bin.(2018).Cyclopeptide RA-V Inhibits Organ Enlargement and Tumorigenesis Induced by YAP Activation.CANCERS,10(11),18.
MLA Ji, Xinyan,et al."Cyclopeptide RA-V Inhibits Organ Enlargement and Tumorigenesis Induced by YAP Activation".CANCERS 10.11(2018):18.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Ji, Xinyan]'s Articles
[Song, Lihua]'s Articles
[Sheng, Li]'s Articles
Baidu academic
Similar articles in Baidu academic
[Ji, Xinyan]'s Articles
[Song, Lihua]'s Articles
[Sheng, Li]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Ji, Xinyan]'s Articles
[Song, Lihua]'s Articles
[Sheng, Li]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.