Density-dependent ERK MAPK expression regulates MMP-9 and influences growth

Mol Cell Biochem. 2019 Jun;456(1-2):115-122. doi: 10.1007/s11010-019-03496-w. Epub 2019 Jan 28.


Previous work has shown that expression of the extracellular signal-regulated kinase (ERK) is decreased by high density in normal fibroblast cells, and this was correlated with increased expression of mitogen-activated protein kinase phosphatases. Because of these differences in ERK regulation upon contact inhibition, it is likely that other cellular responses may be influenced by the attainment of a contact-inhibited state. Expression of matrix metalloproteinase-9 and cadherin cleavage were both found to be decreased upon reaching high culture density. Inhibition of ERK activity with the MEK inhibitor PD98059 resulted in increased expression of cadherins, while constitutive activation of ERK through the use of expression of an ERK construct with a D319N sevenmaker mutation resulted in decreased expression of cadherins and enhanced colony formation of HT-1080 fibrosarcoma cells. Taken together, these results corroborate a role for the regulation of ERK upon the attainment of a contact-inhibited state with increased expression of cadherins.

Keywords: Cadherin; Contact inhibition; ERK; MMP-9.

MeSH terms

  • Cell Line, Tumor
  • Extracellular Signal-Regulated MAP Kinases / biosynthesis*
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Fibrosarcoma / enzymology*
  • Fibrosarcoma / genetics
  • Fibrosarcoma / pathology
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MAP Kinase Signaling System*
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / genetics
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics


  • Neoplasm Proteins
  • Extracellular Signal-Regulated MAP Kinases
  • MMP9 protein, human
  • Matrix Metalloproteinase 9