Core fucosylation of E-cadherin enhances cell-cell adhesion in human colon carcinoma WiDr cells.
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.
Osumi
Daisuke
D
Department of Biochemistry, Osaka University Graduate School of Medicine, Osaka, Japan.
Takahashi
Motoko
M
Miyoshi
Eiji
E
Yokoe
Shunichi
S
Lee
Seung Ho
SH
Noda
Katsuhisa
K
Nakamori
Shoji
S
Gu
Jianguo
J
Ikeda
Yoshitaka
Y
Kuroki
Yoshio
Y
Sengoku
Kazuo
K
Ishikawa
Mutsuo
M
Taniguchi
Naoyuki
N
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
D015820:Cadherins; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase