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

• DOI: 10.18632/oncotarget.5547
• Publication Date: 2015-10-16T05:29:17Z
• Authors: Yong-Qiang Liu; Xiao-Lu Wang; Xin Cheng; Yong-Zhi Lu; Gui-Zhen Wang; Xin-Chun Li; Jian Zhang; Zhe-Sheng Wen; Zhi-Liang Huang; Qin-Lei Gao; Li-Na Yang; Yong-Xian Cheng; Sheng-Ce Tao; Jinsong Liu; Guang-Biao Zhou
• Keywords: Skp1; SKP2

// Yong-Qiang Liu 1, * , Xiao-Lu Wang Xin Cheng Yong-Zhi Lu 2, Gui-Zhen Xin-Chun Li 1 Jian Zhang 3 Zhe-Sheng Wen 4 Zhi-Liang Huang Qin-Lei Gao 5 Li-Na Yang 6 Yong-Xian Sheng-Ce Tao Jinsong 2 Guang-Biao Zhou State Key Laboratory of Membrane Biology, Institute Zoology, Chinese Academy Sciences & University Sciences, Beijing 100101, China Respiratory Disease, Guangzhou Biomedicine and Health, 510530, School Life Anhui University, Hefei 230039, Department Thoracic Surgery, the Cancer Hospital, Sun Yat-Sen 510080, Phytochemistry Plant Resources in West China, Kunming Botany, 650201, Shanghai Center for Systems Biomedicine, (Ministry Education), Jiao Tong 200240, These authors have contributed equally to this work Correspondence to: Zhou, e-mail: [e-mail] Liu, [e-mail] Cheng, [e-mail] Keywords: Skp1, lung cancer, structure-based high-throughput virtual screening, inhibitors, 6-O-angeloylplenolin Received: July 17, 2015      Accepted: September 10, Published: October 12, 2015 ABSTRACT Skp1 is an essential adaptor protein Skp1-Cul1-F-box complex able stabilize conformation some ubiquitin E3 ligases. However, role plays during tumorigenesis remains unclear Skp1-targeting agent lacking. Here we showed that was overexpressed 36/64 (56.3%) non-small cell cancers, elevated associated with poor prognosis. By found molecules including a natural compound 6- O -angeloylplenolin (6-OAP). 6-OAP bound at sites critical Skp1-Skp2 interaction, leading dissociation proteolysis oncogenic ligases NIPA, Skp2, β-TRCP, accumulation their substrates Cyclin B1, P27 E-Cadherin. induced prometaphase arrest exerted potent anti-lung cancer activity two murine models low adverse effect. results indicate pathogenesis, inhibitor inactivates crucial exhibits significant therapeutic potentials.