title: Matrilysin (MMP-7) degrades VE-cadherin and accelerates accumulation of beta-catenin in the nucleus of human umbilical vein endothelial cells.
abstract: 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.
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Japan. yasu0514@med.yokoham-cu.ac.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Momiyama
authors.forename: Masako
authors.initials: M
authors.lastname: Kamiyama
authors.forename: Harumi
authors.initials: H
authors.lastname: Sakurada
authors.forename: Ryusei
authors.initials: R
authors.lastname: Matsuyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Chishima
authors.forename: Yohei
authors.initials: Y
authors.lastname: Hamaguchi
authors.forename: Shoichi
authors.initials: S
authors.lastname: Fujii
authors.forename: Shuji
authors.initials: S
authors.lastname: Saito
authors.forename: Kaori
authors.initials: K
authors.lastname: Kubota
authors.forename: Shingo
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ike
authors.forename: Shigeo
authors.initials: S
authors.lastname: Oki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimada
mesh_terms: 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
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D020783:Matrix Metalloproteinase 7; D051176:beta Catenin; D000099152:Cadherin 5; C060932:MMP7 protein, human