期刊
CELL REPORTS
卷 22, 期 9, 页码 2442-2454出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.02.007
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资金
- Ministry of Science and Technology of China [2014CB542601]
- Natural Science Foundation of China [31521091, 31601131, 31671454, 31622036]
- Wuhan University [2042017kf0199, 2042017kf0242]
- State Key Laboratory of Veterinary Etiological Biology [SKLVEB2017KFKT004]
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.
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