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学科主题临床医学
The essential role of TNIK gene amplification in gastric cancer growth
Yu, D-H1; Zhang, X.1; Wang, H.1,2; Zhang, L.3; Chen, H.4; Hu, M.1; Dong, Z.1; Zhu, G.1; Qian, Z.1; Fan, J.1; Su, X.1; Xu, Y.1; Zheng, L.1; Dong, H.1; Yin, X.1; Ji, Q.1; Ji, J.3
关键词Gastric Cancer Tnik Wnt
刊名ONCOGENESIS
2014-02-01
DOI10.1038/oncsis.2014.2
3
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]NCK-INTERACTING KINASE ; SIGNAL-TRANSDUCTION ; WNT ; CYTOSKELETON ; APOPTOSIS ; AUTOPHAGY ; PATHWAY
英文摘要

Traf2- and Nck-interacting kinase (TNIK) is one of the germinal center kinase family members involved in cytoskeleton organization and neuronal dendrite extension. Emerging evidence supports that TNIK is essential for activation of WNT signaling pathway in colon cancer growth. To search for novel genetic aberrations that drive carcinogenesis, we performed microarray-based comparative hybridization assay for gene copy number variations in primary tumor samples. Our data showed that TNIK gene was amplified in 7% (8/106) of Chinese gastric cancer patients. Theses amplifications were confirmed by fluorescence in situ hybridization analysis. PAMC82 human gastric cancer and T47D human breast cancer cell lines with TNIK amplification were identified to further understand the function of TNIK gene amplification. RNA-interference-mediated silencing of TNIK resulted in significant inhibition of cell growth and induction of cell death in TNIK-amplified, but not in TNIK-non-amplified, cell lines tested. This selective sensitivity to the TNIK inhibition was also observed under the effect of a small-molecule TNIK inhibitor. Furthermore, our data indicated that TNIK′s role in gastric cancer growth was not dependent on Wnt signaling but rather was involved in AKT activation and cell autophagy. Together, our results suggest that TNIK is a novel therapeutic target in gastric cancer and TNIK amplification can be potentially used for patient selection.

语种英语
WOS记录号WOS:000348443300005
引用统计
被引频次:11[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50885
专题北京大学临床肿瘤学院_肿瘤外科
作者单位1.AstraZeneca, Innovat Ctr China, Shanghai, Peoples R China
2.Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China
3.Peking Univ Canc Hosp & Inst, Dept Surg, Key Lab Carcinogenesis & Translat Res, Minist Educ, Beijing 10042, Peoples R China
4.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Gen Surg, Shanghai 200030, Peoples R China
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GB/T 7714
Yu, D-H,Zhang, X.,Wang, H.,et al. The essential role of TNIK gene amplification in gastric cancer growth[J]. ONCOGENESIS,2014,3.
APA Yu, D-H.,Zhang, X..,Wang, H..,Zhang, L..,Chen, H..,...&Ji, J..(2014).The essential role of TNIK gene amplification in gastric cancer growth.ONCOGENESIS,3.
MLA Yu, D-H,et al."The essential role of TNIK gene amplification in gastric cancer growth".ONCOGENESIS 3(2014).
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