title: Expression of N-Acetylglucosaminyltransferase III Suppresses α2,3-Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed to α2,6-Sialylation Levels.
abstract: N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. Overexpression of GnT-III inhibited migration in multiple types of tumor cells. However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. Here, we present evidence that these inconsistencies are mainly attributed to the different expression pattern of cell sialylation. In detail, we show that overexpression of GnT-III significantly inhibits α2,3-sialylation but not α2,6-sialylation. The migratory ability of cells without or with a low level of α2,6-sialylation is consistently suppressed after GnT-III overexpression. In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. Interestingly, up-regulation of α2,6-sialylation by overexpressing β-galactoside α2,6-sialyltranferase 1 in the α2,6-hyposialylated HeLa-S3 cells abolishes the anti-migratory effects of GnT-III. Conversely, depletion of α2,6-sialylation by knock-out of β-galactoside α2,6-sialyltranferase 1 in α2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. Taken together, our data clearly demonstrate that high expression of α2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis.
authors.affiliation: From the Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aobaku, Sendai, Miyagi, 981-8558 and.
authors.forename: Jishun
authors.initials: J
authors.lastname: Lu
authors.affiliation: From the Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aobaku, Sendai, Miyagi, 981-8558 and.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Isaji
authors.affiliation: From the Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aobaku, Sendai, Miyagi, 981-8558 and.
authors.forename: Sanghun
authors.initials: S
authors.lastname: Im
authors.affiliation: From the Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aobaku, Sendai, Miyagi, 981-8558 and.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: the Department of Life Science and Biotechnology, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kameyama
authors.affiliation: From the Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aobaku, Sendai, Miyagi, 981-8558 and. Electronic address: jgu@tohoku-pharm.ac.jp.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Gu
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D055786:Gene Knockout Techniques; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D017351:N-Acetylglucosaminyltransferases; D012799:Sialyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
keywords: N-linked glycosylation; bisecting GlcNAc; cell migration; glycosyltransferase; integrin; sialyltransferase