Prometastatic effect of N-acetylglucosaminyltransferase V is due to modification and stabilization of active matriptase by adding β1-6 GlcNAc branching

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Title
Prometastatic effect of N-acetylglucosaminyltransferase V is due to modification and stabilization of active matriptase by adding β1-6 GlcNAc branching
Author(s)
Shinji Ihara; Eiji Miyoshi; Jeong Heon Ko; Kohei Murata; Susumu Nakahara; Koichi Honke; Robert B Dickson; Chen Yong Lin; Naoyuki Taniguchi
Bibliographic Citation
Journal of Biological Chemistry, vol. 277, no. 19, pp. 16960-16967
Publication Year
2002
Abstract
Oligosaccharide moieties of glycoproteins are structurally altered during development, carcinogenesis, and malignant transformations. It is well known that β1-6 GlcNAc branching, a product of UDP-GlcNAc α-mannoside β1-6-N-acetylglucosaminyltransferase (GnT-V), is associated with malignant transformation as the results of such alterations. However, the mechanism by which β1-6 GlcNAc branching is linked to metastasis remains unclear, because the identification of specific glycoprotein(s) that are glycosylated by GnT-V and its biological function have not been examined. We herein report that matriptase, which activates both urokinase-type plasminogen activator and hepatocyte growth factor, is a target protein for GnT-V. The overexpression of GnT-V in gastric cancer cells leads to severe peritoneal dissemination in athymic mice, which can be attributed to the increased expression of matriptase. This increase was due to the acquired resistance of matriptase to degradation, since it is glycosylated by GnT-V and a corresponding increase in the active form. These results indicate that this process is a key element in malignant transformation, as the direct result of oligosaccharide modification.
ISSN
0021-9258
Publisher
Amer Soc Biochemistry Molecular Biology Inc
DOI
http://dx.doi.org/10.1074/jbc.M200673200
Type
Article
Appears in Collections:
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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