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

CORC > 昆明植物研究所 > 中国科学院昆明植物研究所 > 植物化学与西部植物资源持续利用国家重点实验室

	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
刊名	ONCOTARGET
	2015-10-27
卷号	6 期号:33 页码:34953-34967
关键词	Skp1 lung cancer structure-based high-throughput virtual screening inhibitors 6-O-angeloylplenolin
英文摘要	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.
类目[WOS]	Oncology ; Cell Biology
研究领域[WOS]	Oncology ; Cell Biology
关键词[WOS]	F-BOX PROTEINS ; UBIQUITIN-LIGASE COMPLEX ; E3 LIGASE ; CELL-CYCLE ; CENTIPEDA-MINIMA ; BREAST-CANCER ; MITOTIC EXIT ; BETA-CATENIN ; IN-VITRO ; DEGRADATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000366107200081
内容类型	期刊论文
源URL	[http://ir.kib.ac.cn/handle/151853/25261]
专题	昆明植物研究所_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.