Inhibition of p38/MK2 Signaling Prevents Vascular Invasion of Melanoma

J Invest Dermatol. 2020 Apr;140(4):878-890.e5. doi: 10.1016/j.jid.2019.08.451. Epub 2019 Oct 14.


Melanoma cells can switch between distinct gene expression profiles, resulting in proliferative or invasive phenotypes. Signaling pathways involved in this switch were analyzed by gene expression profiling of a cohort of 22 patient-derived melanoma cell lines. CDH1 negativity was identified as a surrogate marker for the invasive phenotype. CDH1 expression could be turned on and off by modulating activity of p38 or its downstream target MK2, suggesting that this pathway controls melanoma progression. Mechanistically, MK2 inhibition prevented melanoma-induced vascular barrier disruption, reduced the expression of PODXL and DEL-1, and prevented vascular dissemination in vivo. PODXL and DEL-1 expression in patients with melanoma were associated with poor survival and thus can be used as prognostic markers. Downstream targets of MK2 may thus serve as candidate therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Neoplasm Invasiveness
  • Prognosis
  • Signal Transduction
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Tumor Cells, Cultured
  • Vascular Neoplasms / metabolism
  • Vascular Neoplasms / pathology
  • Vascular Neoplasms / prevention & control*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / genetics


  • p38 Mitogen-Activated Protein Kinases