Knockdown of Nemo‑like kinase promotes metastasis in non‑small‑cell lung cancer.

The evolutionarily conserved serine/threonine kinase Nemo-like kinase (NLK) serves an important role in cell proliferation, migration, invasion and apoptosis by regulating transcription factors among various cancers. In the present study, the function of NLK in human non-small cell lung cancer (NSCLC) was investigated. Immunohistochemical analysis and western blotting demonstrated that NLK expression was significantly reduced in NSCLC tissues compared with corresponding peritumoral tissues. Statistical analysis revealed that decreased NLK expression was associated with the presence of primary tumors, tumor node metastasis (TNM) staging, differentiation, lymph node metastasis, and E-cadherin and vimentin expression. Univariate analysis indicated that NLK expression, differentiation, lymph node metastasis, TNM stage, and E-cadherin and vimentin expression affected the prognosis of NSCLC. Cox regression analyses revealed NLK expression and TNM as independent factors that affected prognosis. Kaplan-Meier survival analysis revealed that patients with NSCLC and low NLK expression had relatively shorter durations of overall survival. In vitro, NLK overexpression inhibited A549 ncell migration and invasion as determined by wound healing and Transwell migration assays, respectively. Additionally, immunofluorescence staining indicated that downregulation of NLK expression could induce epithelial-mesenchymal transition in NSCLC. NLK knockdown significantly decreased the expression of the epithelial marker E-cadherin, and markedly increased that of beta-catenin and the mesenchymal marker vimentin. Furthermore, NLK was reported to directly interact with beta-catenin as determined by a co-immunoprecipitation assay. Collectively, the results of the present study indicated that decreased NLK expression could promote tumor metastasis in NSCLC.