Deeping in the Role of the MAP-Kinases Interacting Kinases (MNKs) in Cancer

Int J Mol Sci. 2020 Apr 23;21(8):2967. doi: 10.3390/ijms21082967.

Abstract

The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are involved in oncogenic transformation and can promote metastasis and tumor progression. In human cells, there are four MNKs isoforms (MNK1a/b and MNK2a/b), derived from two genes by alternative splicing. These kinases play an important role controlling the expression of specific proteins involved in cell cycle, cell survival and cell motility via eukaryotic initiation factor 4E (eIF4E) regulation, but also through other substrates such as heterogeneous nuclear ribonucleoprotein A1, polypyrimidine tract-binding protein-associated splicing factor and Sprouty 2. In this review, we provide an overview of the role of MNK in human cancers, describing the studies conducted to date to elucidate the mechanism involved in the action of MNKs, as well as the development of MNK inhibitors in different hematological cancers and solid tumors.

Keywords: MNK; antitumor drug; cancer; eIF4E; metastasis; therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Biomarkers
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Disease Susceptibility
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / etiology
  • Neoplasms / metabolism*
  • Neoplasms / mortality
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Intracellular Signaling Peptides and Proteins
  • Protein Kinase Inhibitors
  • Protein Serine-Threonine Kinases