Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Department of Respiratory Medicine, The Sixth People's Hospital of Nantong, Nantong, Jiangsu 226001, P.R. China.
Oncol Rep. 2019 Sep;42(3):1090-1100. doi: 10.3892/or.2019.7226. Epub 2019 Jul 9.
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 β‑catenin and the mesenchymal marker vimentin. Furthermore, NLK was reported to directly interact with β‑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.
进化上保守的丝氨酸/苏氨酸激酶 Nemo 样激酶 (NLK) 通过调节各种癌症中的转录因子，在细胞增殖、迁移、侵袭和凋亡中发挥重要作用。本研究探讨了 NLK 在人非小细胞肺癌 (NSCLC) 中的作用。免疫组织化学分析和 Western blot 表明，NLK 表达在 NSCLC 组织中明显低于相应的癌旁组织。统计学分析显示，NLK 表达降低与原发性肿瘤、肿瘤淋巴结转移 (TNM) 分期、分化、淋巴结转移以及 E-钙黏蛋白和波形蛋白表达有关。单因素分析表明，NLK 表达、分化、淋巴结转移、TNM 分期以及 E-钙黏蛋白和波形蛋白表达影响 NSCLC 的预后。Cox 回归分析显示 NLK 表达和 TNM 是影响预后的独立因素。Kaplan-Meier 生存分析显示，NLK 低表达的 NSCLC 患者总生存期相对较短。在体外，通过划痕愈合和 Transwell 迁移实验分别证实 NLK 过表达抑制 A549 细胞迁移和侵袭。此外，免疫荧光染色表明，下调 NLK 表达可诱导 NSCLC 上皮-间充质转化。NLK 敲低显著降低上皮标志物 E-钙黏蛋白的表达，显著增加 β-连环蛋白和间充质标志物波形蛋白的表达。此外，通过共免疫沉淀实验证实 NLK 与 β-连环蛋白直接相互作用。综上所述，本研究结果表明，NLK 表达降低可促进 NSCLC 肿瘤转移。
