Silencing NACK by siRNA inhibits tumorigenesis in non-small cell lung cancer via targeting Notch1 signaling pathway.

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung tumor with poor prognosis, in which the Notch signaling pathway plays an important role. Notch activation complex kinase (NACK) has been reported both as a co-activator and a target gene of the Notch pathway. However, the molecular mechanism of NACK in NSCLC still remains unknown. In this study, the expression of NACK was analyzed in 35 paired NSCLC tumor samples and 2 NSCLC cell lines. MTT assay, cell migration assay, cell invasion assay, flow cytometry assay, and xenograft model were employed to detect the effect of NACK knockdown on the cell proliferation, metastasis, invasion and apoptosis of NSCLC. The relationship between NACK and Notch1 signaling pathway in NSCLC cells was assessed by western blot and luciferase reporter assay. We found that the expression of NACK in the NSCLC tissues and lung cancer cells were significantly increased. High level of NACK expression is remarkable associated with tumor differentiation, lymphatic metastasis, clinical stage and poor survival prognosis. The interference of NACK significantly inhibited cell proliferation, invasion and metastasis through inducing apoptosis in NSCLC cells. The transcriptional activity of related Notch1 target genes were significantly suppressed resulting from NACK knockdown. This study demonstrates that interference of NACK inhibits NSCLC progression through Notch1 signaling pathway and targeting NACK may be an effective approach for NSCLC therapy.