title: Enhanced epithelial-mesenchymal transition-like phenotype in N-acetylglucosaminyltransferase V transgenic mouse skin promotes wound healing.
abstract: N-Acetylglucosaminyltransferase V (GnT-V) catalyzes the β1,6 branching of N-acetylglucosamine on N-glycans. GnT-V expression is elevated during malignant transformation in various types of cancer. However, the mechanism by which GnT-V promotes cancer progression is unclear. To characterize the biological significance of GnT-V, we established GnT-V transgenic (Tg) mice, in which GnT-V is regulated by a β-actin promoter. No spontaneous cancer was detected in any organs of the GnT-V Tg mice. However, GnT-V expression was up-regulated in GnT-V Tg mouse skin, and cultured keratinocytes derived from these mice showed enhanced migration, which was associated with changes in E-cadherin localization and epithelial-mesenchymal transition (EMT). Further, EMT-associated factors snail, twist, and N-cadherin were up-regulated, and cutaneous wound healing was accelerated in vivo. We further investigated the detailed mechanisms of EMT by assessing EGF signaling and found up-regulated EGF receptor signaling in GnT-V Tg mouse keratinocytes. These findings indicate that GnT-V overexpression promotes EMT and keratinocyte migration in part through enhanced EGF receptor signaling.
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Terao
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakahara
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kimura
authors.forename: Arisa
authors.initials: A
authors.lastname: Kato
authors.forename: Kenta
authors.initials: K
authors.lastname: Moriwaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kamada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murota
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
mesh_terms: D000117:Acetylglucosamine / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D012867:Skin / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D014945:Wound Healing
chemical_list: D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; D066246:ErbB Receptors; D000117:Acetylglucosamine