Cyclopeptide RA-V Inhibits Organ Enlargement and Tumorigenesis Induced by YAP Activation
文献类型：期刊论文
| 作者 | Ji, Xinyan6,7; Song, Lihua4,5; Sheng, Li3; Gao, Anhui3; Zhao, Yang6,7; Han, Shixun6,7; Zhang, Yuchao6,7; Zhu, Chu6,7; Zhao, Simeng1; Wang, Zhe4,5 |
| 刊名 | CANCERS
 |
| 出版日期 | 2018-11 |
| 卷号 | 10期号:11 |
| 关键词 | hippo pathway YAP TAZ RA-V cancer organ size protein synthesis |
| ISSN号 | 2072-6694 |
| DOI | 10.3390/cancers10110449 |
| 文献子类 | Article |
| 英文摘要 | The 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. |
| WOS关键词 | TUMOR-SUPPRESSOR PATHWAY ; HIPPO PATHWAY ; SIZE-CONTROL ; CYCLIC HEXAPEPTIDES ; CELL-PROLIFERATION ; TISSUE HOMEOSTASIS ; TEAD/TEF FAMILY ; GROWTH ; TAZ ; BOUVARDIN |
| 资助项目 | National Natural Science Foundation of China[31471316] ; National Natural Science Foundation of China[81730069] ; National Key R&D Program of China[2017YFA0504502] ; National Natural Science Foundation of China International Collaboration Project[31661130150] ; Fundamental Research Funds for the Central Universities[00000000] ; Newton Advanced Fellowship from the Academy of Medical Sciences, UK[00000000] ; National New Drug Innovation Major Project of Ministry of Science and Technology of China[2017ZX09309027] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000451307700056 |
| 出版者 | MDPI |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279505]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物安全性评价中心 |
| 通讯作者 | Li, Jia; Tan, Ninghua; Zhao, Bin |
| 作者单位 | 1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Natl Ctr Drug Screening, 189 Guoshoujing Rd, Shanghai 201203, Peoples R China; 4.China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 211198, Jiangsu, Peoples R China; 5.China Pharmaceut Univ, Sch Tradit Chinese Pharm, Nanjing 211198, Jiangsu, Peoples R China; 6.Zhejiang Univ, Life Sci Inst, Innovat Ctr Cell Signaling Network, Hangzhou 310058, Zhejiang, Peoples R China; 7.Zhejiang Univ, Life Sci Inst, MOE Key Lab Biosyst Homeostasis & Protect, Hangzhou 310058, Zhejiang, Peoples R China; 8.Hangzhou Normal Univ, Inst Aging Res, Hangzhou 311121, Zhejiang, Peoples R China; |
| 推荐引用方式 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). |
| 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). |
| MLA | Ji, Xinyan,et al."Cyclopeptide RA-V Inhibits Organ Enlargement and Tumorigenesis Induced by YAP Activation".CANCERS 10.11(2018). |
入库方式： OAI收割
来源：上海药物研究所
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