| Matrilysin (MMP-7) degrades VE-cadherin and accelerates accumulation of beta-catenin in the nucleus of human umbilical vein endothelial cells |
Authors: Yasushi Ichikawa, Takashi Ishikawa, Nobuyoshi Momiyama, Masako Kamiyama, Harumi Sakurada, Ryusei Matsuyama, Satoshi Hasegawa, Takashi Chishima, Yohei Hamaguchi, Shoichi Fujii, Shuji Saito, Kaori Kubota, Shingo Hasegawa, Hideyuki Ike, Shigeo Oki, Hiroshi Shimada |
Affiliations:
Department of Surgery-2, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. yasu0514@med.yokoham-cu.ac.jp
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Pages: 311-315 |
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.
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