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A novel USP9X substrate TTK contributes to tumorigenesis in non-small-cell lung cancer

文献类型：期刊论文

作者Chen, Xiangling2,3,5; Yu, Chengli2,3,5; Gao, Jing2,3; Zhu, Hongwen2,3; Cui, Binghai4,5; Zhang, Tao1,5; Zhou, Yanting2,3; Liu, Qian2,3,5; He, Han2,3; Xiao, Ruoxuan2,3,5
刊名THERANOSTICS
出版日期2018
卷号8期号:9页码:2348-2360
关键词non-small cell lung cancer (NSCLC) quantitative proteomics deubiquitinase USP9X TTK
ISSN号1838-7640
DOI10.7150/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关键词DEUBIQUITINASE INHIBITION ; CHROMOSOMAL INSTABILITY ; UBIQUITIN LIGASES ; STABILITY ; EXPRESSION ; KINASE ; MPS1 ; PROLIFERATION ; DEGRADATION ; CENTROSOME
资助项目National Key Research and Development Program from the Ministry of Science and Technology of China[2017YFC1700200] ; National Natural Science Foundation of China[21375138] ; National Natural Science Foundation of China[31570830] ; "one hundred talent program" of Chinese Academy of Sciences[00000000] ; Chinese Academy of Sciences[XDA12030203] ; Innovation Project of Instrument and Equipment Function Development from the Bureau of Goods, Chinese Academy of Sciences[YZ201542]
WOS研究方向Research & Experimental Medicine
语种英语
WOS记录号WOS:000428234800004
出版者IVYSPRING INT PUBL
源URL[http://119.78.100.183/handle/2S10ELR8/272323]  
专题分析化学研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Zhou, Hu
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai 201203, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China;
4.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;
5.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.,Cui, Binghai.,...&Zhou, Hu.(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.

入库方式： OAI收割

来源：上海药物研究所

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