Core fucosylation of E-cadherin enhances cell–cell adhesion in human colon carcinoma WiDr cells |
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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 |
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| Affiliation: | Department of Biochemistry, Osaka University Graduate School of Medicine, Osaka;;Department of Obstetrics and Gynecology, Asahikawa Medical College, Asahikawa;;Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo;;Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita;;Department of Surgery, National Osaka Hospital, Osaka;;Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai;;Division of Molecular Cell Biology, Department of Biomolecular Sciences, Saga University Faculty of Medicine, Saga;;Department of Disease Glycomics, Research Institute for Microbial Diseases, Center for Advanced Science and Innovation, Osaka University, Suita;;Systems Glycobiology Group, Disease Glycomics Team, RIKEN Advanced Science Institute, Wako, Japan |
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| Abstract: | α1,6‐Fucosyltransferase (Fut8), an enzyme that catalyzes the introduction of α1,6 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 α1,6‐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 α1,6‐fucosyltransferase and E‐cadherin expression, we introduced α1,6‐fucosyltransferase in WiDr human colon carcinoma cells. It was revealed that the low molecular weight population of E‐cadherin was significantly increased in α1,6‐fucosyltransferase‐transfected WiDr cells in dense culture, which resulted in an enhancement in cell–cell adhesion. The transfection of mutated α1,6‐fucosyltransferase with no enzymatic activity had no effect on E‐cadherin expression, indicating that core fucosylation is involved in the phenomena. In α1,6‐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 α1,6‐fucosyltransferase into kidney epithelial cells from α1,6‐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 α1,6‐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. (Cancer Sci 2009; 100: 888–896) |
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