Nemo-like kinase (NLK) is an evolutionarily conserved MAP kinase–related kinase involved
in the pathogenesis of several human cancers. We examined the expression of NLK in lung
cancer tissues through western blot analysis. We enhanced or knocked down NLK expression by
gene transfection or RNA interference, respectively, in lung cancer cells and examined expression
alterations of key proteins in the Wnt signaling pathway and in epithelial–mesenchymal transition
(EMT). We also examined the roles of NLK in the proliferation and invasiveness of lung cancer
cells by cell proliferation, colony formation, and Matrigel invasion assays. NLK expression was
found to be significantly higher in lung cancer tissue samples than in corresponding healthy lung tissue
samples. Overexpression of NLK correlated with poor prognosis of patients with lung cancer.
Overexpression of NLK upregulated β-catenin, TCF4, and Wnt target genes such as cyclin D1, c-
Myc, and MMP7. N-cadherin and TWIST, the key proteins in EMT, were upregulated, while Ecadherin
expression was reduced. Additionally, proliferation, colony formation, and invasion turned
out to be enhanced in NLK-overexpressing cells. After NLK knockdown in lung cancer cells, we obtained
the opposite results. In conclusion, NLK is overexpressed in lung cancers and indicates poor
prognosis. Overexpression of NLK activates the Wnt signaling pathway and EMT and promotes the
proliferation and invasiveness of lung cancer cells.