Matrilysin (MMP-7) degrades VE-cadherin and accelerates accumulation of beta-catenin in the nucleus of human umbilical vein endothelial cells.
Matrilysin, MMP-7, is an important target for anti-metastasis therapy of colorectal cancer because it is a strong proteolytic factor secreted from the cancer cell itself and it induces tumor angiogenesis. In a previous report, we showed that matrilysin accelerated human umbilical vein endothelial cell (HUVEC) proliferation in low serum conditioned medium. In the present study, we show that matrilysin stimulation decreased VE-cadherin expression, induced accumulation of beta-catenin in the nucleus of the HUVEC, and up-regulated matrilysin mRNA expression. These results compel a hypothesis that matrilysin cleaves VE-cadherin and releases beta-catenin from the VE-cadherin/catenin complex; the free beta-catenin can activate T-cell factor (Tcf) DNA binding protein, which accelerates cell proliferation and matrilysin expression.
Ichikawa
Yasushi
Y
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Japan. yasu0514@med.yokoham-cu.ac.jp
Ishikawa
Takashi
T
Momiyama
Nobuyoshi
N
Kamiyama
Masako
M
Sakurada
Harumi
H
Matsuyama
Ryusei
R
Hasegawa
Satoshi
S
Chishima
Takashi
T
Hamaguchi
Yohei
Y
Fujii
Shoichi
S
Saito
Shuji
S
Kubota
Kaori
K
Hasegawa
Shingo
S
Ike
Hideyuki
H
Oki
Shigeo
S
Shimada
Hiroshi
H
D015703:Antigens, CD; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology; D051176:beta Catenin / Q000378:metabolism*; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D020783:Matrix Metalloproteinase 7; D051176:beta Catenin; D000099152:Cadherin 5; C060932:MMP7 protein, human