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USP2a Supports Metastasis by Tuning TGF-beta Signaling
Zhao, Yin1; Wang, Xiaomeng1,2; Wang, Qingqing3; Deng, Yu5; Li, Kang1,2; Zhang, Man1,2; Zhang, Qiang1,2; Zhou, Jin2; Wang, Hong-Yan2; Bai, Peng2; Ren, Yujie1,2; Zhang, Ni5; Li, Weina6; Cheng, Yongbo7; Xiao, Wuhan8; Du, Hai-Ning2; Cheng, Xiaoliang7; Yin, Lei2; Fu, Xiangning4; Lin, Dandan4; Zhou, Qianghui3; Zhong, Bo1,2
2018-02-27
Source PublicationCELL REPORTS
ISSN2211-1247
Volume22Issue:9Pages:2442-2454
Abstract

TGF-beta has been demonstrated to promote tumor metastasis, and the regulatory mechanisms are poorly understood. Here, we report the role of USP2a in promoting metastasis by facilitating TGF-beta-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-beta stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1. The phosphorylation of USP2a and SMAD2 is positively correlated in human tumor biopsies, and USP2a is hyper-phosphorylated in lung adenocarcinomas with lymph node invasion. Depletion or pharmacologic inhibition of USP2a dampens TGF-beta-triggered signaling and metastasis. Our findings have characterized an essential role of USP2a as a potential target for treatment of metastatic cancers.

DOI10.1016/j.celrep.2018.02.007
Funding OrganizationMinistry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; 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Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; 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Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology
Indexed BySCI
Language英语
Funding ProjectMinistry of Science and Technology of China[2014CB542601] ; Natural Science Foundation of China[31521091] ; Natural Science Foundation of China[31601131] ; Natural Science Foundation of China[31671454] ; Natural Science Foundation of China[31622036] ; Wuhan University[2042017kf0199] ; Wuhan University[2042017kf0242] ; State Key Laboratory of Veterinary Etiological Biology[SKLVEB2017KFKT004]
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000426243000019
WOS KeywordUBIQUITIN-SPECIFIC PROTEASE ; CYCLIN D1 DEGRADATION ; I RECEPTOR ; PROSTATE-CANCER ; ACTIVATION ; GROWTH ; DOMAIN ; SMAD2 ; GLIOBLASTOMA ; RECOGNITION
PublisherCELL PRESS
Funding OrganizationMinistry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; Wuhan University ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; State Key Laboratory of Veterinary Etiological Biology ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Natural Science Foundation of China ; Wuhan University ; Wuhan University ; Wuhan University ; 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Citation statistics
Cited Times:9[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/29917
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorZhong, Bo
Affiliation1.Wuhan Univ, Sch Med, Med Res Inst, Wuhan 430071, Hubei, Peoples R China
2.Wuhan Univ, Coll Life Sci, Wuhan 430072, Hubei, Peoples R China
3.Wuhan Univ, Coll Chem & Mol Sci, Wuhan 430072, Hubei, Peoples R China
4.Wuhan Univ, Renmin Hosp, Canc Ctr, Wuhan 430060, Hubei, Peoples R China
5.Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Thorac Surg, Wuhan 430030, Hubei, Peoples R China
6.Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept & Inst Infect Dis, Wuhan 430030, Hubei, Peoples R China
7.Wuhan Qlife Lab Co, Wuhan 430074, Hubei, Peoples R China
8.Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China
Recommended Citation
GB/T 7714		 Zhao, Yin,Wang, Xiaomeng,Wang, Qingqing,et al. USP2a Supports Metastasis by Tuning TGF-beta Signaling[J]. CELL REPORTS,2018,22(9):2442-2454.
APA Zhao, Yin.,Wang, Xiaomeng.,Wang, Qingqing.,Deng, Yu.,Li, Kang.,...&Zhong, Bo.(2018).USP2a Supports Metastasis by Tuning TGF-beta Signaling.CELL REPORTS,22(9),2442-2454.
MLA Zhao, Yin,et al."USP2a Supports Metastasis by Tuning TGF-beta Signaling".CELL REPORTS 22.9(2018):2442-2454.
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