Core fucosylation of E-cadherin enhances cell-cell adhesion in human colon carcinoma WiDr cells.
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| 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.
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| Authors | Daisuke Osumi, Motoko Takahashi, Eiji Miyoshi, Shunichi Yokoe, Seung Ho Lee, Katsuhisa Noda, Shoji Nakamori, Jianguo Gu, Yoshitaka Ikeda, Yoshio Kuroki, Kazuo Sengoku, Mutsuo Ishikawa, Naoyuki Taniguchi |
| Journal | Cancer science (Cancer Sci) Vol. 100 Issue 5 Pg. 888-95 (May 2009) ISSN: 1349-7006 [Electronic] England |
| PMID | 19302290 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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