Membrane type 1-matrix metalloproteinase expression is regulated by E-cadherin through the suppression of mitogen-activated protein kinase cascade.
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.
First Department of Oral Surgery, School of Dentistry, Hokkaido University, Kita 13 Nishi 7, kita-ku, 060-8586, Sapporo, Japan. arara@den.hokudai.ac.jp
T
T
Ara
Y
Y
Deyama
Y
Y
Yoshimura
F
F
Higashino
M
M
Shindoh
A
A
Matsumoto
H
H
Fukuda
D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D017931:DNA Primers; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D015534:Trans-Activators; D014162:Transfection; D014407:Tumor Cells, Cultured; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D019716:Tissue Inhibitor of Metalloproteinase-2; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1