SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling pathways
Abstract Background The 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. Methods The differential proteome between human gliom...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-07-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12964-019-0392-9 |
| _version_ | 1819144775916322816 |
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| author | Yanfang Yang Ziwei Liang Zijing Xia Xixi Wang Yanni Ma Zenghua Sheng Qingjia Gu Guobo Shen Liangxue Zhou Hongxia Zhu Ningzhi Xu Shufang Liang |
| author_facet | Yanfang Yang Ziwei Liang Zijing Xia Xixi Wang Yanni Ma Zenghua Sheng Qingjia Gu Guobo Shen Liangxue Zhou Hongxia Zhu Ningzhi Xu Shufang Liang |
| author_sort | Yanfang Yang |
| collection | DOAJ |
| description | Abstract Background The 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. Methods The 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. Results SAE1 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. Conclusion SAE1 promotes glioma cancer progression via enhancing Akt SUMOylation-mediated signaling pathway, which indicates targeting SUMOylation is a promising therapeutic strategy for human glioma. |
| first_indexed | 2024-12-22T12:47:30Z |
| format | Article |
| id | doaj.art-5af56e3dc71949718dc1c5b58fae6876 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-12-22T12:47:30Z |
| publishDate | 2019-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-5af56e3dc71949718dc1c5b58fae68762022-12-21T18:25:16ZengBMCCell Communication and Signaling1478-811X2019-07-0117111410.1186/s12964-019-0392-9SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling pathwaysYanfang Yang0Ziwei Liang1Zijing Xia2Xixi Wang3Yanni Ma4Zenghua Sheng5Qingjia Gu6Guobo Shen7Liangxue Zhou8Hongxia Zhu9Ningzhi Xu10Shufang Liang11State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for BiotherapyState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for BiotherapyDepartment of Rheumatology and Immunology, West China Hospital, Sichuan UniversityState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for BiotherapyState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for BiotherapyState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for BiotherapyDepartment of Otorhinolaryngology, University of Electronic Science and Technology of China, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s HospitalState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for BiotherapyState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for BiotherapyLaboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical SciencesState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for BiotherapyState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for BiotherapyAbstract Background The 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. Methods The 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. Results SAE1 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. Conclusion SAE1 promotes glioma cancer progression via enhancing Akt SUMOylation-mediated signaling pathway, which indicates targeting SUMOylation is a promising therapeutic strategy for human glioma.http://link.springer.com/article/10.1186/s12964-019-0392-9GliomaSAE1SUMOylationPhosphorylationAkt signaling pathway |
| spellingShingle | Yanfang Yang Ziwei Liang Zijing Xia Xixi Wang Yanni Ma Zenghua Sheng Qingjia Gu Guobo Shen Liangxue Zhou Hongxia Zhu Ningzhi Xu Shufang Liang SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling pathways Cell Communication and Signaling Glioma SAE1 SUMOylation Phosphorylation Akt signaling pathway |
| title | SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling pathways |
| title_full | SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling pathways |
| title_fullStr | SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling pathways |
| title_full_unstemmed | SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling pathways |
| title_short | SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling pathways |
| title_sort | sae1 promotes human glioma progression through activating akt sumoylation mediated signaling pathways |
| topic | Glioma SAE1 SUMOylation Phosphorylation Akt signaling pathway |
| url | http://link.springer.com/article/10.1186/s12964-019-0392-9 |
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