دورية أكاديمية
The essential role of TNIK gene amplification in gastric cancer growth
| العنوان: | The essential role of TNIK gene amplification in gastric cancer growth |
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| المؤلفون: | Yu, D-H, Zhang, X., Wang, H., Zhang, L., Chen, H., Hu, M., Dong, Z., Zhu, G., Qian, Z., Fan, J., Su, X., Xu, Y., Zheng, L., Dong, H., Yin, X., Ji, Q., Ji, J. |
| المساهمون: | Yu, DH (reprint author), Astrazeneca, Biosci, 199 Liangjing Rd,Zhangjiang High Tech Pk, Shangha 201203, Peoples R China., AstraZeneca, Innovat Ctr China, Shanghai, Peoples R China., Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China., Peking Univ Canc Hosp & Inst, Dept Surg, Key Lab Carcinogenesis & Translat Res, Minist Educ, Beijing 10042, Peoples R China., Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Gen Surg, Shanghai 200030, Peoples R China., Astrazeneca, Biosci, 199 Liangjing Rd,Zhangjiang High Tech Pk, Shangha 201203, Peoples R China. |
| المصدر: | SCI ; PubMed |
| سنة النشر: | 2014 |
| المجموعة: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| مصطلحات موضوعية: | gastric cancer, TNIK, Wnt, NCK-INTERACTING KINASE, SIGNAL-TRANSDUCTION, CYTOSKELETON, APOPTOSIS, AUTOPHAGY, PATHWAY |
| الوصف: | 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. ; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000348443300005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Test ; Oncology ; SCI(E) ; PubMed ; 10 ; ARTICLE ; yudehua@yahoo.com; jiafuj@gmail.com ; e89 ; 3 |
| نوع الوثيقة: | journal/newspaper |
| اللغة: | English |
| تدمد: | 2157-9024 |
| العلاقة: | ONCOGENESIS.2014,3.; 653544; http://hdl.handle.net/20.500.11897/342372Test; WOS:000348443300005 |
| DOI: | 10.1038/oncsis.2014.2 |
| الإتاحة: | https://doi.org/20.500.11897/342372Test https://doi.org/10.1038/oncsis.2014.2Test https://hdl.handle.net/20.500.11897/342372Test |
| رقم الانضمام: | edsbas.DF457AA |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 21579024 |
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| DOI: | 10.1038/oncsis.2014.2 |