TRAF2/Nck-interacting Kinase (TNIK)-A Potential Nove Target For Oncogenesis

Traf2- and Nck-interacting kinase (TNIK) is one of germinal centre kinase (GCK) family members involved in cytoskeleton organization and neuronal dendrite extension. Emerging evidence supports an essential role of TNIK in activation of WNTsingaling pathway and colon cancer growth. To search for novel genetic aberrations that drive carcinogenesis, we performed microarray-based comparative hybridization (aGCH) assay to screen 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 (FISH) analysis. To further understand the function of TNIK gene amplification, PAMC82 human gastric cancer and T47D breast cancer cell lines with TNIK amplification were identified. RNA-interference-mediated silencing of TNIK resulted in significantly reduced cell growth and increased cell death in the TNIK amplified, but not in the non-amplified, tested cell lines. This selective sensitivity to TNIK inhibition was also observed by using a small molecule inhibitor. Furthermore our data indicated that the requirement of TNIK in gastric cancer growth was Wnt signaling independent, but rather involved in AKT activation and cell autophage. Together, our results suggest that TNIK is a novel therapeutic target in gastric cancer and TNIK amplification can be potentially used for patient selection.