MAP kinase-interacting serine/threonine kinase 2 promotes proliferation, metastasis, and predicts poor prognosis in non-small cell lung cancer

Sci Rep. 2017 Sep 6;7(1):10612. doi: 10.1038/s41598-017-10397-9.

Abstract

We hypothesized that MAP kinase-interacting serine/threonine kinase 2 (MNK2) may contribute to non-small cell lung cancer (NSCLC) development, and serve as a new therapeutic target. Immunohistochemical staining evaluated the correlation between MNK2 expression and clinicopathological features in 367 NSCLC cancer tissues. We determined the effects of MNK2 silencing in NSCLC cell lines in vitro and in vivo. RT-PCR and western blotting was used to examine the impact of MNK2 on ERK and AKT pathways. MNK2 was overexpressed in NSCLC cell lines and tumor tissues. Patients with MNK2 overexpression had lower OS rates (P < 0.001). High expression of MNK2 was correlated with lymph node metastasis (P = 0.008). MNK2 functioned as an independent prognostic factor for poor survival in patients with NSCLC (P = 0.003). MNK2 down-regulation inhibited proliferation, migration and invasion in vitro (P < 0.001), and reduced tumor growth and invasion in nude mice (P < 0.05). MNK2 enhanced phosphorylation of eIF4E, a downstream target of ERK and AKT pathways, which promoted NSCLC proliferation and invasion. We conclude that MNK2 overexpression in NSCLC is associated with proliferation, migration, invasion, and lower survival rates in patients via the phosphorylated eIF4E-mediated signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Clonal Evolution
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Neoplasm Metastasis
  • Prognosis
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • MKNK2 protein, human
  • Protein-Serine-Threonine Kinases