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DOI | 10.1038/s41467-018-05138-z |
Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7 | |
Zhang, Zhengkui1,2; Fan, Yao1,2; Xie, Feng3,4; Zhou, Hang1,2; Jin, Ke1,2; Shao, Li5; Shi, Wenhao6,7,8,9; Fang, Pengfei1,2; Yang, Bing10,11; van Dam, Hans12,13; ten Dijke, Peter12,13; Zheng, Xiaofeng14; Yan, Xiaohua15; Jia, Junling1,2; Zheng, Min5; Jin, Jin1,2; Ding, Chen6,7,8,9; Ye, Sheng1,2; Zhou, Fangfang3,4; Zhang, Long1,2 | |
2017-12-13 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China; USA; Netherlands |
英文摘要 | Metastasis is the main cause of death in cancer patients. TGF-beta is pro-metastatic for malignant cancer cells. Here we report a loss-of-function screen in mice with metastasis as readout and identify OTUD1 as a metastasis-repressing factor. OTUD1-silenced cancer cells show mesenchymal and stem-cell-like characteristics. Further investigation reveals that OTUD1 directly deubiquitinates the TGF-beta pathway inhibitor SMAD7 and prevents its degradation. Moreover, OTUD1 cleaves Lysine 33-linked poly-ubiquitin chains of SMAD7 Lysine 220, which exposes the SMAD7 PY motif, enabling SMURF2 binding and subsequent T beta RI turnover at the cell surface. Importantly, OTUD1 is lost in multiple types of human cancers and loss of OTUD1 increases metastasis in intracardial xenograft and orthotopic transplantation models, and correlates with poor prognosis among breast cancer patients. High levels of OTUD1 inhibit cancer stemness and shut off metastasis. Thus, OTUD1 represses breast cancer metastasis by mitigating TGF-beta-induced pro-oncogenic responses via deubiquitination of SMAD7. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000417884500022 |
WOS关键词 | TGF-BETA RECEPTOR ; E3 UBIQUITIN LIGASE ; NF-KAPPA-B ; K33-LINKED POLYUBIQUITINATION ; TUMOR-CELLS ; STEM-CELLS ; GENE ; DEGRADATION ; MONOUBIQUITINATION ; ANTAGONIST |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203899 |
专题 | 资源环境科学 |
作者单位 | 1.Zhejiang Univ, Inst Life Sci, Hangzhou 310058, Zhejiang, Peoples R China; 2.Zhejiang Univ, Innovat Ctr Cell Signalling Network, Hangzhou 310058, Zhejiang, Peoples R China; 3.Soochow Univ, Inst Biol, Suzhou 215123, Peoples R China; 4.Soochow Univ, Inst Med Sci, Suzhou 215123, Peoples R China; 5.Zhejiang Univ, Affiliated Hosp 1, State Key Lab Diagnost & Treatment Infect Dis, Sch Med,Collaborat Innovat Ctr Diag & Treatment I, Hangzhou 310000, Zhejiang, Peoples R China; 6.Beijing Inst Radiat Med, Beijing Proteome Res Ctr, State Key Lab Prote, Beijing 100039, Peoples R China; 7.Natl Ctr Prot Sci, Beijing 102206, Peoples R China; 8.Fudan Univ, Inst Biomed Sci, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China; 9.Fudan Univ, Inst Biomed Sci, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, Shanghai 200433, Peoples R China; 10.Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA; 11.Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA; 12.Leiden Univ, Med Ctr, Dept Mol Cell Biol, Postbus 9600, NL-2300 RC Leiden, Netherlands; 13.Leiden Univ, Med Ctr, Canc Genom Ctr Netherlands, Postbus 9600, NL-2300 RC Leiden, Netherlands; 14.Univ Texas MD Anderson Canc Ctr, Metastasis Res Ctr, Dept Canc Biol, Houston, TX 77054 USA; 15.Tsinghua Univ, Beijing 100084, Peoples R China |
推荐引用方式 GB/T 7714 | Zhang, Zhengkui,Fan, Yao,Xie, Feng,et al. Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Zhang, Zhengkui.,Fan, Yao.,Xie, Feng.,Zhou, Hang.,Jin, Ke.,...&Zhang, Long.(2017).Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7.NATURE COMMUNICATIONS,8. |
MLA | Zhang, Zhengkui,et al."Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7".NATURE COMMUNICATIONS 8(2017). |
条目包含的文件 | 条目无相关文件。 |
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