机构：[1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital,Sichuan University, and Collaborative Innovation Center for Biotherapy,No.17, 3rd Section of People’s South Road, Chengdu 610041, People’sRepublic of China四川大学华西医院[2]Department of Rheumatology and Immunology, WestChina Hospital, Sichuan University, Chengdu 610041, Sichuan, People’sRepublic of China[3]Department of Otorhinolaryngology, University ofElectronic Science and Technology of China, Sichuan Academy of MedicalSciences & Sichuan Provincial People’s Hospital, Chengdu, China四川省人民医院[4]Department of Neurosurgery, West China Hospital, Sichuan University,Chengdu 610041, Sichuan, People’s Republic of China四川大学华西医院[5]Laboratory of Celland Molecular Biology & State Key Laboratory of Molecular Oncology, CancerInstitute & Cancer Hospital, Chinese Academy of Medical Sciences, Beijing100034, People’s Republic of China.
BackgroundThe SUMO-activating enzyme SAE1 is indispensable for protein SUMOylation. A dysregulation of SAE1 expression involves in progression of several human cancers. However, its biological roles of SAE1 in glioma are unclear by now.MethodsThe differential proteome between human glioma tissues and para-cancerous brain tissues were identified by LC-MS/MS. SAE1 expression was further assessed by immunohistochemistry. The patient overall survival versus SAE1 expression level was evaluated by Kaplan-Meier method. The glioma cell growth and migration were evaluated under SAE1 overexpression or inhibition by the CCK8, transwell assay and wound healing analysis. The SUMO1 modified target proteins were enriched from total cellular or tissue proteins by incubation with the anti-SUMO1 antibody on protein-A beads overnight, then the SUMOylated proteins were detected by Western blot. Cell apoptosis and cell cycle were analyzed by flow cytometry. The nude mouse xenograft was determined glioma growth and tumorigenicity in vivo.ResultsSAE1 is identified to increase in glioma tissues by a quantitative proteomic dissection, and SAE1 upregulation indicates a high level of tumor malignancy grade and a poor overall survival for glioma patients. SAE1 overexpression induces an increase of the SUMOylation and Ser473 phosphorylation of AKT, which promotes glioma cell growth in vitro and in nude mouse tumor model. On the contrary, SAE1 silence induces an obvious suppression of the SUMOylation and Ser473 phosphorylation of Akt, which inhibits glioma cell proliferation and the tumor xenograft growth through inducing cell cycle arrest at G2 phase and cell apoptosis driven by serial biochemical molecular events.ConclusionSAE1 promotes glioma cancer progression via enhancing Akt SUMOylation-mediated signaling pathway, which indicates targeting SUMOylation is a promising therapeutic strategy for human glioma.
基金：
National 863 High Tech FoundationNational High Technology Research and Development Program of China [2014AA020608]; National Natural Sciences Foundation of ChinaNational Natural Science Foundation of China [31470810]; Health Commission of Sichuan Province [17ZD045]; Chengdu Science and Technology Program [2017-GH02-00062-HZ]
第一作者机构：[1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital,Sichuan University, and Collaborative Innovation Center for Biotherapy,No.17, 3rd Section of People’s South Road, Chengdu 610041, People’sRepublic of China
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推荐引用方式(GB/T 7714)：
Yanfang Yang,Ziwei Liang,Zijing Xia,et al.SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling pathways[J].CELL COMMUNICATION AND SIGNALING.2019,17:doi:10.1186/s12964-019-0392-9.
APA：
Yanfang Yang,Ziwei Liang,Zijing Xia,Xixi Wang,Yanni Ma...&Shufang Liang.(2019).SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling pathways.CELL COMMUNICATION AND SIGNALING,17,
MLA：
Yanfang Yang,et al."SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling pathways".CELL COMMUNICATION AND SIGNALING 17.(2019)
