Glycobiology Advance Access published online on September 20, 2007
Glycobiology, doi:10.1093/glycob/cwm094
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A high expression of GDP-fucose transporter in hepatocellular carcinoma is a key factor for increases in fucosylation
1 Department of Molecular Biochemistry & Clinical Investigation Osaka University Graduate School of Medicine 1–7, Yamada-oka, Suita, Osaka 565–0871 Japan
2 Osaka Rosai Hospital, 1179–3, Nagasone-cho, Kita-ku, Sakai, Osaka 591–8025 Japan
3 Department of Glycotherapeutics Osaka University Graduate School of Medicine 2–2, Yamada-oka, Suita, Osaka 565–0871 Japan
4 Department of Biochemistry Osaka University Graduate School of Medicine 2–2, Yamada-oka, Suita, Osaka 565–0871 Japan
5 Department of Disease Glycomics, Research Institute for Microbial Diseases Osaka University, Center for Advanced Science & Innovation 2–1, Yamada-oka Suita, Osaka 565–0871 Japan
6 Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine 2–2, Yamada-oka, Suita, Osaka 565–0871 Japan
* To whom correspondence should be addressed. Phone & FAX: +81-6-6879-2590; E-mail: emiyoshi{at}sahs.med.osaka-u.ac.jp
Received on April 27, 2007; accepted on August 31, 2007
Changes in the levels of fucosylation regulate a biological phenotype of cancer cells and a specific fucosylation such as fucosylated 
-fetoprotein (AFP-L3) has been clinically used as a tumor marker for hepatocellular carcinoma (HCC). However, detailed molecular mechanisms that explain the increased fucosylation in HCC remain unknown despite 10-years of study by these researchers. Fucosylation is regulated by complicated mechanisms that involve several factors: fucosyltransferases, GDP-fucose transporter (GDP-Fuc Tr) and synthetic enzymes of GDP-fucose such as GDP-mannose 4, 6-dehydratase (GMD), GDP-4-keto-6-deoxy-mannose-3, 5-epimerase-4-reductase (FX) and GDP-fucose pyrophosphorylase. In this study, the expression of fucosylation-related genes in HCC tissues was studied and it was found that GDP-Fuc Tr is a key factor for increases in fucosylation. A real-time RT-PCR analysis showed significant increases in GDP-Fuc Tr and FX expression in HCC, and levels of the GMD protein were up-regulated by post-translational modification in HCC tissues. In vitro cell experiments showed that the level of GDP-Fuc Tr was the most significantly correlated with the level of cellular fucosylation and the over-expression of GDP-Fuc Tr dramatically increased fucosylation in Hep3B cells. The importance of GDP-Fuc Tr in the increase of fucosylation observed was also confirmed with immunohistochmical analyses. These findings suggest that the up-regulation of GDP-Fuc Tr plays a pivotal role in increased fucosylation in HCC and represents an attractive target for new treatments and diagnosis for HCC.
Key words: AFP-L3 / fucose / GDP-fucose / GDP-fucose transporter / hepatocellular carcinoma
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  E. Miyoshi, K. Moriwaki, and T. Nakagawa Biological Function of Fucosylation in Cancer Biology J. Biochem., June 1, 2008; 143(6): 725 - 729. [Abstract] [Full Text] [PDF]
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