title: Prometastatic effect of N-acetylglucosaminyltransferase V is due to modification and stabilization of active matriptase by adding beta 1-6 GlcNAc branching.
abstract: Oligosaccharide moieties of glycoproteins are structurally altered during development, carcinogenesis, and malignant transformations. It is well known that beta1-6 GlcNAc branching, a product of UDP-GlcNAc alpha-mannoside beta1-6-N-acetylglucosaminyltransferase (GnT-V), is associated with malignant transformation as the results of such alterations. However, the mechanism by which beta1-6 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.
authors.affiliation: Department of Biochemistry, Osaka University Medical School/Graduate School of Medicine, B1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ihara
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.forename: Jeong Heon
authors.initials: JH
authors.lastname: Ko
authors.forename: Kohei
authors.initials: K
authors.lastname: Murata
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakahara
authors.forename: Koichi
authors.initials: K
authors.lastname: Honke
authors.forename: Robert B
authors.initials: RB
authors.lastname: Dickson
authors.forename: Chen-Yong
authors.initials: CY
authors.lastname: Lin
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004848:Epithelium / Q000201:enzymology; D005434:Flow Cytometry; D005647:Fucosyltransferases / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism / Q000494:pharmacology*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D017830:Octoxynol / Q000494:pharmacology; D009844:Oligosaccharides / Q000737:chemistry; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014357:Trypsin / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D017077:Culture Media, Conditioned; D037102:Lectins; D008565:Membrane Proteins; D009844:Oligosaccharides; D017830:Octoxynol; D005647:Fucosyltransferases; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; C020559:Glycoprotein 6-alpha-L-fucosyltransferase; D012697:Serine Endopeptidases; C485595:matriptase; C485596:ST14 protein, human; C118992:St14 protein, mouse; D014357:Trypsin; D000117:Acetylglucosamine