| 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 Publication | ONCOTARGET
 |
| Volume | 6Issue:33Pages:34953-34967 |
| Abstract | Skp1 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. |
| Keyword | Skp1 Lung Cancer Structure-based High-throughput Virtual Screening Inhibitors 6-o-angeloylplenolin |
| Indexed By | SCI |
| Language | 英语 |
| WOS Research Area | Oncology ; Cell Biology |
| WOS Subject | Oncology ; Cell Biology |
| WOS ID | WOS:000366107200081 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://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. |
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| 5547-94324-1-PB.pdf（2162KB） | 期刊论文 | 作者接受稿 | 开放获取 | CC BY-NC-SA | View Download | |
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