Membrane type 1-matrix metalloproteinase expression is regulated by E-cadherin through the suppression of mitogen-activated protein kinase cascade

Cancer Lett. 2000 Sep 1;157(2):115-21. doi: 10.1016/s0304-3835(00)00494-8.

Abstract

To elucidate the role of E-cadherin in matrix metalloproteinases (MMPs) expression, we transfected to squamous carcinoma cells with E-cadherin cDNA. HN5 cells and mock-transfected HN5-neo cells expressed proMMP-2 and active MMP-2. E-cadherin-transfected HN5-EC cells produced comparable proMMP-2 but low active MMP-2; and membrane type 1-MMP (MT1-MMP) mRNA declined. Phosphorylated ERK, a marker of mitogen-activated protein (MAP) kinase cascade, also declined in HN5-EC cells. The addition of anti-E-cadherin antibody resulted in the disappearance of these alterations in HN5-EC cells. These results suggest that E-cadherin suppresses MAP kinase cascade and down-regulates MT1-MMP.

MeSH terms

  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / metabolism*
  • Cytoskeletal Proteins / metabolism
  • DNA Primers
  • DNA, Complementary / metabolism
  • Down-Regulation
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Signaling System*
  • Matrix Metalloproteinase 1 / biosynthesis
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism*
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Precipitin Tests
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Trans-Activators*
  • Transfection
  • Tumor Cells, Cultured
  • alpha Catenin
  • beta Catenin

Substances

  • CTNNA1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • DNA Primers
  • DNA, Complementary
  • RNA, Messenger
  • Trans-Activators
  • alpha Catenin
  • beta Catenin
  • Tissue Inhibitor of Metalloproteinase-2
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 1