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A High Expression of GDP-Fucose Transporter in Hepatocellular Carcinoma is a Key Factor for Increases in Fucosylation

A High Expression of GDP-Fucose Transporter in Hepatocellular Carcinoma is a Key Factor for... Changes in the levels of fucosylation regulate the biological phenotype of cancer cells and a specific fucosylation, such as fucosylated α-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 reverse transcription polymerase chain reaction (RT-PCR) analysis showed significant increases in GDP-Fuc Tr and FX expression in HCC, and levels of the GMD protein were upregulated by posttranslational 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 overexpression of GDP-Fuc Tr dramatically increased fucosylation in Hep3B cells. The importance of GDP-Fuc Tr in the increase of fucosylation was also confirmed with immunohistochemical analyses. These findings suggest that the upregulation 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Glycobiology Oxford University Press

A High Expression of GDP-Fucose Transporter in Hepatocellular Carcinoma is a Key Factor for Increases in Fucosylation

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References (34)

Publisher
Oxford University Press
Copyright
© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]
Subject
Original Article
ISSN
0959-6658
eISSN
1460-2423
DOI
10.1093/glycob/cwm094
pmid
17884843
Publisher site
See Article on Publisher Site

Abstract

Changes in the levels of fucosylation regulate the biological phenotype of cancer cells and a specific fucosylation, such as fucosylated α-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 reverse transcription polymerase chain reaction (RT-PCR) analysis showed significant increases in GDP-Fuc Tr and FX expression in HCC, and levels of the GMD protein were upregulated by posttranslational 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 overexpression of GDP-Fuc Tr dramatically increased fucosylation in Hep3B cells. The importance of GDP-Fuc Tr in the increase of fucosylation was also confirmed with immunohistochemical analyses. These findings suggest that the upregulation 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.

Journal

Glycobiology – Oxford University Press

Published: Dec 20, 2007

Keywords: Keywords AFP-L3 fucose GDP-fucose GDP-fucose transporter hepatocellular carcinoma

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