Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors
Liu,Yong-Qiang; Wang,Xiao-Lu; Cheng,Xin; Lu,Yong-Zhi; Wang,Gui-Zhen; Li,Xin-Chun; Zhang,Jian; Wen,Zhe-Sheng; Huang,Zhi-Liang; Gao,Qin-Lei; Yang,Li-Na; Cheng,Yong-Xian; Tao,Sheng-Ce; Liu,Jinsong; Zhou,Guang-Biao
2015-10-27
Source PublicationONCOTARGET
Volume6Issue:33Pages:34953-34967
AbstractSkp1 is an essential adaptor protein of the Skp1-Cul1-F-box protein complex and is able to stabilize the conformation of some ubiquitin E3 ligases. However, the role Skp1 plays during tumorigenesis remains unclear and Skp1-targeting agent is lacking. Here we showed that Skp1 was overexpressed in 36/64 (56.3%) of non-small cell lung cancers, and elevated Skp1 was associated with poor prognosis. By structure-based high-throughput virtual screening, we found some Skp1-targeting molecules including a natural compound 6-O-angeloylplenolin (6-OAP). 6-OAP bound Skp1 at sites critical to Skp1-Skp2 interaction, leading to dissociation and proteolysis of oncogenic E3 ligases NIPA, Skp2, and beta-TRCP, and accumulation of their substrates Cyclin B1, P27 and E-Cadherin. 6-OAP induced prometaphase arrest and exerted potent anti-lung cancer activity in two murine models and showed low adverse effect. These results indicate that Skp1 is critical to lung cancer pathogenesis, and Skp1 inhibitor inactivates crucial oncogenic E3 ligases and exhibits significant therapeutic potentials.
KeywordSkp1 Lung Cancer Structure-based High-throughput Virtual Screening Inhibitors 6-o-angeloylplenolin
Indexed BySCI
Language英语
WOS Research AreaOncology ; Cell Biology
WOS SubjectOncology ; Cell Biology
WOS IDWOS:000366107200081
Citation statistics
Cited Times:18[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/25261
Collection植物化学与西部植物资源持续利用国家重点实验室
Recommended Citation
GB/T 7714
Liu,Yong-Qiang,Wang,Xiao-Lu,Cheng,Xin,et al. Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors[J]. ONCOTARGET,2015,6(33):34953-34967.
APA Liu,Yong-Qiang.,Wang,Xiao-Lu.,Cheng,Xin.,Lu,Yong-Zhi.,Wang,Gui-Zhen.,...&Zhou,Guang-Biao.(2015).Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors.ONCOTARGET,6(33),34953-34967.
MLA Liu,Yong-Qiang,et al."Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors".ONCOTARGET 6.33(2015):34953-34967.
Files in This Item: Download All
File Name/Size DocType Version Access License
5547-94324-1-PB.pdf(2162KB)期刊论文作者接受稿开放获取CC BY-NC-SAView Download
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Liu,Yong-Qiang]'s Articles
[Wang,Xiao-Lu]'s Articles
[Cheng,Xin]'s Articles
Baidu academic
Similar articles in Baidu academic
[Liu,Yong-Qiang]'s Articles
[Wang,Xiao-Lu]'s Articles
[Cheng,Xin]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Liu,Yong-Qiang]'s Articles
[Wang,Xiao-Lu]'s Articles
[Cheng,Xin]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: 5547-94324-1-PB.pdf
Format: Adobe PDF
All comments (0)
No comment.
 

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