A novel USP9X substrate TTK contributes to tumorigenesis in non-small-cell lung cancer | |
Chen, Xiangling1,4; Yu, Chengli1,4; Gao, Jing1; Zhu, Hongwen1; Zhou, Yanting1; Liu, Qian1,4; He, Han1; Xiao, Ruoxuan1,4; Zhou, Hu1,4; Cui, Binghai2,4 | |
刊名 | THERANOSTICS |
2018 | |
卷号 | 8期号:9页码:2348-2360 |
关键词 | Deubiquitinase Inhibition Chromosomal Instability Ubiquitin Ligases Stability Expression Kinase Mps1 Proliferation Degradation Centrosome |
ISSN号 | 1838-7640 |
DOI | 10.7150/thno.22901 |
文献子类 | Article |
英文摘要 | The X-linked deubiquitinase, USP9X, is implicated in multiple cancers by targeting various substrates. Increased expression of USP9X is observed in non-small-cell lung cancer (NSCLC) and is correlated with poor prognosis. However, the molecular mechanism for USP9X regulation of tumor cell survival and tumorigenesis in NSCLC is less defined. Methods: In this study, chemical labeling, quantitative proteomic screening was applied to analyze A549 cells with or without USP9X RNA interference. Functional in vitro and in vivo experiments were performed to confirm the oncogenic effects of USP9X in NSCLC and to investigate the underlying mechanisms. Results: The resulting data suggested that dual specificity protein kinase TTK is a potential substrate of USP9X. Further experimental evidences confirmed that USP9X stabilized TTK via direct interaction and efficient deubiquitination of TTK on K48 ubiquitin chain. Moreover, knockdown of USP9X or TTK inhibited cell proliferation, migration and tumorigenesis, and the immunohistochemical analysis of clinical NSCLC samples showed that the protein expression levels of USP9X and TTK were significantly elevated and positively correlated in tumor tissues. Conclusions: In summary, our data demonstrated that the USP9X-TTK axis may play a critical role in NSCLC, and could be considered as a potential therapeutic target. |
WOS研究方向 | Medicine, Research & Experimental |
语种 | 英语 |
WOS记录号 | WOS:000428234800004 |
内容类型 | 期刊论文 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/3373] |
专题 | 生化所2018年发文 上海生化细胞研究所_上海生科院生化细胞研究所 |
通讯作者 | Zhou, Hu |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, CAS Key Lab Syst Biol,Inst Biochem & Cell Biol, Shanghai Inst Biol Sci,Innovat Ctr Cell Signaling, Shanghai 200031, Peoples R China; 4.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China |
推荐引用方式 GB/T 7714 | Chen, Xiangling,Yu, Chengli,Gao, Jing,et al. A novel USP9X substrate TTK contributes to tumorigenesis in non-small-cell lung cancer[J]. THERANOSTICS,2018,8(9):2348-2360. |
APA | Chen, Xiangling.,Yu, Chengli.,Gao, Jing.,Zhu, Hongwen.,Zhou, Yanting.,...&Xie, Hua.(2018).A novel USP9X substrate TTK contributes to tumorigenesis in non-small-cell lung cancer.THERANOSTICS,8(9),2348-2360. |
MLA | Chen, Xiangling,et al."A novel USP9X substrate TTK contributes to tumorigenesis in non-small-cell lung cancer".THERANOSTICS 8.9(2018):2348-2360. |
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