Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors

	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
发表期刊	ONCOTARGET
卷号	6 期号:33 页码:34953-34967
摘要	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.
关键词	Skp1 Lung Cancer Structure-based High-throughput Virtual Screening Inhibitors 6-o-angeloylplenolin
收录类别	SCI
语种	英语
WOS记录号	WOS:000366107200081
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/25261
专题	植物化学与西部植物资源持续利用国家重点实验室
推荐引用方式 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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