| First Author | Zhao Y | Year | 2018 |
| Journal | Cell Rep | Volume | 22 |
| Issue | 9 | Pages | 2442-2454 |
| PubMed ID | 29490279 | Mgi Jnum | J:271128 |
| Mgi Id | MGI:6278824 | Doi | 10.1016/j.celrep.2018.02.007 |
| Citation | Zhao Y, et al. (2018) USP2a Supports Metastasis by Tuning TGF-beta Signaling. Cell Rep 22(9):2442-2454 |
| abstractText | 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. |
