MAPKAPK2 plays a crucial role in the progression of head and neck squamous cell carcinoma by regulating transcript stability

J Exp Clin Cancer Res. 2019 Apr 25;38(1):175. doi: 10.1186/s13046-019-1167-2.

Abstract

Background: Head and neck squamous-cell carcinoma (HNSCC) ranks sixth among cancers worldwide. Though several molecular mechanisms of tumor initiation and progression of HNSCC are known, others remain unclear. Significance of p38/MAPKAPK2 (Mitogen-activated protein kinase-activated protein kinase-2) pathway in cell stress and inflammation is well established and its role in tumor development is being widely studied.

Methods: We have elucidated the role of MAPKAPK2 (MK2) in HNSCC pathogenesis using clinical tissue samples, MK2-knockdown (MK2KD) cells and heterotropic xenograft mice model.

Results: In patient-derived tissue samples, we observed that MK2 is reproducibly overexpressed. Increased stability of cyclin-dependent kinase inhibitor 1B (p27), mitogen-activated protein kinase phosphatase-1 (MKP-1) transcripts and decreased half-life of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) transcripts in MK2KD cells suggests that MK2 regulates their transcript stability. In vivo xenograft experiments established that knockdown of MK2 attenuates course of tumor progression in immunocompromised mice.

Conclusion: Altogether, MK2 is responsible for regulating the transcript stability and is functionally important to modulate HNSCC pathogenesis.

Keywords: HNSCC; MAPKAPK2; Pathogenesis; RBPs; Transcript stability; Xenograft.

MeSH terms

  • Animals
  • Cell Proliferation / genetics*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Dual Specificity Phosphatase 1 / genetics
  • Humans
  • Inflammation / genetics*
  • Inflammation / pathology
  • Intracellular Signaling Peptides and Proteins / genetics*
  • MAP-Kinase-Activated Kinase 2
  • Mice
  • Proliferating Cell Nuclear Antigen / genetics
  • Protein Serine-Threonine Kinases / genetics*
  • RNA, Messenger / genetics
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Tumor Necrosis Factor-alpha / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Cyclin-Dependent Kinase Inhibitor p27
  • Dual Specificity Phosphatase 1
  • Intracellular Signaling Peptides and Proteins
  • Proliferating Cell Nuclear Antigen
  • Protein Serine-Threonine Kinases
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • MAP-Kinase-Activated Kinase 2
  • VEGFA protein, human
  • p27 antigen
  • DUSP1 protein, human