Core fucosylation of E‐cadherin enhances cell–cell adhesion in human colon carcinoma WiDr cells

Abstract

a1,6-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 a1,6-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 cellcell 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 Nglycosidase 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: 888-895) I t is generally accepted that glycosylation affects many properties of glycoproteins, including their conformation, flexibility, and hydrophilicity. As a result, it regulates protein sorting, stability, and protein-protein interactions.(1-5) N-Glycans have a common core structure, and their branching patterns are determined by glycosyltransferases.(6,7) Fut8 is an enzyme that catalyzes the introduction of α1,6 core fucose on the asparagine-branched N-acetylglucosamine residue of the chitobiose unit of complextype N-glycans. (8,9) Fut8 has been investigated especially in terms of oncogenesis, since the α1,6-fucosylation of α-fetoprotein is a well-known marker of hepatocellular carcinoma. (10) In previous studies, our group reported that Fut8 expression is markedly enhanced in several types of cancer cell lines (11) rat hepatoma tissues (12) and in ovarian serous adenocarcinoma cells.E-cadherin is a 120 kDa type I membrane protein, which belongs to the class of calcium-dependent cell adhesion molecules. (14) It mediates cell-cell adhesi...

Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer

“…This discrepancy can be due to the expression of E-cadherin, which is detected in Hep3B but not these aggressive lung cancer cell lines we used. E-cadherin is a calcium-dependent cell-cell adhesion molecule with a pivotal role in tumor suppression (30), and it has been reported that core fucosylation of E-cadherin can enhance cell-cell adhesion in human colon carcinoma cells (10). Therefore, overexpressing FUT8 in Hep3B cell, an epithelial-type cell, which is positive in E-cadherin expression, may strengthen Ecadherin-mediated cell-cell interaction and reduce the metastatic abilities of FUT8 transfectants.…”

“…Lacking the core fucose on these receptors leads to a marked reductions in ligand binding ability and downstream signaling. Furthermore, the increase in core fucosylation on E-cadherin has been shown to strengthen cell-cell adhesion (10).…”

Roles of Fucosylation in Tumor Immunology

“…In fact, the expression of these determinants in epithelial cancer has been reported to correlate with the poor prognosis of human colon cancer (23). In addition, α1-6 fucosylation (core fucosylation) is crucial for the functions of several growth factor receptors, such as EGF (24) and TGF-β receptors (25), and adhesion molecules, such as integrins (26) and E-cadherin (27). Core fucosylation is very closely involved in the biological behavior of cancer cells through regulation of the functions of these membraneassociated receptors (28).…”

GDP-mannose-4,6-dehydratase (GMDS) Deficiency Renders Colon Cancer Cells Resistant to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Receptor- and CD95-mediated Apoptosis by Inhibiting Complex II Formation

“…Fucosylation involves the attachment of an L-fucose residue to an oligosaccharide or protein and is one of the most important oligosaccharide modifications in cancer (13). Most cell surface receptors, including epidermal growth factor receptor (14), transforming growth factor-␤ receptor (15), E-cadherin (16), and integrins (17), are fucosylated. Fucosylated oligosaccharides regulate many physiological and pathological events, including cell growth, migration, embryogenesis, and tumor invasion, by affecting the folding and structure of these cell surface receptors (18).…”