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Deubiquitinase USP29 promotes gastric cancer cell migration by cooperating with phosphatase SCP1 to stabilize Snail protein

文献类型：期刊论文

作者Qian, Wenli1; Li, Qi1,2; Wu, Xinglong3; Li, Wenguo4,5; Li, Qiwei6; Zhang, Jie1; Li, Mengying1; Zhang, Dan1; Zhao, Hongxia7; Zou, Xiuqun1
刊名ONCOGENE
出版日期2020-09-24
页码14
ISSN号0950-9232
DOI10.1038/s41388-020-01471-0
通讯作者Zhang, Lingqiang(zhanglq@nic.bmi.ac.cn) ; Yang, Xiao-Dong(xdyang@shsmu.edu.cn) ; Hou, Zhaoyuan(houzy@sjtu.edu.cn)
英文摘要Snail is a master inducer of epithelial-mesenchymal transition (EMT) and metastasis, however, Snail protein is labile and is quickly degraded through the predominate ubiquitination-mediated proteasome pathway. Deubiquitinases (DUBs) can counteract the Snail degradation process to maintain high level of Snail protein in cancer cells. In this study, we screened a cDNA library containing 79 DUBs, and discovered that a panel of DUBs consisting of USP13, USP28, USP29, USP37, OTUD6A, and DUB3 can markedly stabilize Snail protein, with USP29 displaying the strongest activity to prevent Snail degradation. Mechanistically, USP29 enhances the interaction of Snail and SCP1, resulting in simultaneous dephosphorylation and deubiquitination of Snail and thereafter cooperative prevention of Snail degradation. Biologically, ectopic expression of USP29 promotes gastric cancer cell migration, and depletion of Snail abolishes USP29-mediated cell migration; and USP29 can be induced by major EMT and metastatic inducing factors such as TGF beta, TNF alpha, and hypoxia. More importantly, high expression levels of Snail, USP29, and SCP1 are associated with poor survival and prognosis. Collectively, these data indicate that Snail is a crucial substrate for USP29 to promote cell migration and USP29/SCP1 complex may be new therapeutic targets to treat metastatic cancer.
WOS关键词TERMINAL DOMAIN PHOSPHATASE ; E-CADHERIN REPRESSION ; DNA-REPLICATION ; GENE ; TRANSCRIPTION ; PHOSPHORYLATION ; RECRUITMENT ; METASTASIS ; DROSOPHILA ; DISTINCT
资助项目National Natural Science Foundation of China[81872131] ; National Natural Science Foundation of China[31671415] ; National Natural Science Foundation of China[31570770] ; National Natural Science Foundation of China[31770818]
WOS研究方向Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
语种英语
WOS记录号WOS:000572607300002
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/291238]  
专题新药研究国家重点实验室
通讯作者Zhang, Lingqiang; Yang, Xiao-Dong; Hou, Zhaoyuan
作者单位1.Shanghai Jiao Tong Univ, Hongqiao Inst Med, Tongren Hosp, Fac Basic Med,Sch Med, Shanghai 200025, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Lanling Peoples Hosp, Cent Clin Lab, Lanling Cty 277700, Shandong, Peoples R China
4.Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Immunol, Dept Immunol & Microbiol, Shanghai 200025, Peoples R China
5.Shanghai Jiao Tong Univ, Sch Med, Minist Educ, Key Lab Cell Death & Differentiat, Shanghai 200025, Peoples R China
6.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Biliary Pancreat Surg, Shanghai 200127, Peoples R China
7.Univ Helsinki, Fac Biol & Environm Sci, Helsinki, Finland
8.Beijing Inst Life, Natl Ctr Prot Sci Beijing, State Key Lab Prote, Beijing 100850, Peoples R China
9.Shanghai Jiao Tong Univ, Dept Biochem & Mol Cell Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Sch Med, Shanghai 200025, Peoples R China
推荐引用方式
GB/T 7714		 Qian, Wenli,Li, Qi,Wu, Xinglong,et al. Deubiquitinase USP29 promotes gastric cancer cell migration by cooperating with phosphatase SCP1 to stabilize Snail protein[J]. ONCOGENE,2020:14.
APA Qian, Wenli.,Li, Qi.,Wu, Xinglong.,Li, Wenguo.,Li, Qiwei.,...&Hou, Zhaoyuan.(2020).Deubiquitinase USP29 promotes gastric cancer cell migration by cooperating with phosphatase SCP1 to stabilize Snail protein.ONCOGENE,14.
MLA Qian, Wenli,et al."Deubiquitinase USP29 promotes gastric cancer cell migration by cooperating with phosphatase SCP1 to stabilize Snail protein".ONCOGENE (2020):14.

入库方式： OAI收割

来源：上海药物研究所

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