title: Core fucosylation of E-cadherin enhances cell-cell adhesion in human colon carcinoma WiDr cells.
abstract: Alpha1,6-fucosyltransferase (Fut8), an enzyme that catalyzes the introduction of alpha1,6 core fucose to the innermost N-acetylglucosamine residue of the N-glycan, has been implicated in the development, immune system, and tumorigenesis. We found that alpha1,6-fucosyltransferase and E-cadherin expression levels are significantly elevated in primary colorectal cancer samples. Interestingly, low molecular weight population of E-cadherin appeared as well as normal sized E-cadherin in cancer samples. To investigate the correlation between alpha1,6-fucosyltransferase and E-cadherin expression, we introduced alpha1,6-fucosyltransferase in WiDr human colon carcinoma cells. It was revealed that the low molecular weight population of E-cadherin was significantly increased in alpha1,6-fucosyltransferase-transfected WiDr cells in dense culture, which resulted in an enhancement in cell-cell adhesion. The transfection of mutated alpha1,6-fucosyltransferase with no enzymatic activity had no effect on E-cadherin expression, indicating that core fucosylation is involved in the phenomena. In alpha1,6-fucosyltransferase knock down mouse pancreatic acinar cell carcinoma TGP49 cells, the expression of E-cadherin and E-cadherin dependent cell-cell adhesion was decreased. The introduction of alpha1,6-fucosyltransferase into kidney epithelial cells from alpha1,6-fucosyltransferase(-/-) mice restored the expression of E-cadherin and E-cadherin-dependent cell-cell adhesion. Based on the results of lectin blotting, peptide N-glycosidase F treatment, and pulse-chase studies, it was demonstrated that the low molecular weight population of E-cadherin contains peptide N-glycosidase F insensitive sugar chains, and the turnover rate of E-cadherin was reduced in alpha1,6-Fucosyltransferase transfectants. Thus, it was suggested that core fucosylation regulates the processing of oligosaccharides and turnover of E-cadherin. These results suggest a possible role of core fucosylation in the regulation of cell-cell adhesion in cancer.
authors.affiliation: Department of Biochemistry, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Osumi
authors.forename: Motoko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yokoe
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Noda
authors.forename: Shoji
authors.initials: S
authors.lastname: Nakamori
authors.forename: Jianguo
authors.initials: J
authors.lastname: Gu
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kuroki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sengoku
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male
chemical_list: D015820:Cadherins; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase