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Significance of α1-6 Fucosylation in Hepatocellular Carcinoma

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Liver Cirrhosis

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Summary

α1-6 Fucosyltransferase (α1-6FucT) catalyzes the transfer of fucose from GDP-Fuc to N-linked type complex glycoproteins. Recently, serum α1-6 fucosylated α-fetoprotein (AFP) has been employed for a differential diagnosis of hepatocellular carcinoma (HCC) from liver cirrhosis. To determine the molecular basis of the fucosylated AFP in the serum of patients with HCC, we have succeeded in the purification and cDNA cloning of α1-6FucT from porcine brain and a gastric cancer cell line, respectively. Their homology is 92.2% at the nucleotide level and 95.7% at the amino acid level. No putative N-glycosylation sites were found in the predicted amino acid sequence. α1-6FucT was widely expressed in various rat tissues except normal liver. Expression of α1-6FucT in the liver was enhanced during hepatocarcinogenesis of LEC rats, which develop hereditary hepatitis and hepatomas. In human liver diseases, α1-6FucT was expressed in both HCCs and their surrounding tissues with chronic liver disease, but not in normal liver. Although serum AFP has been employed for an early diagnosis of patients with HCC, the mechanisms by which α1-6 fucosylation of AFP occurs in HCC seem to be not solely due to the up-regulation of α1-6FucT. Interestingly, when the α1-6FucT gene was transfected into Hep3B, a human hepatoma cell line, tumor formation in the liver of nude mice after splenic injection was dramatically suppressed. The mechanisms of the suppression were due to decreases in cell adhesion through aberrant glycosylation of α5β1 integrin. In this review, we focus on the biological significance of α1-6 fucosylation in HCC.

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Authors and Affiliations

  1. Department of Biochemistry, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Eiji Miyoshi, Katsuhisa Noda & Naoyuki Taniguchi

  2. Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Yutaka Sasaki & Norio Hayashi

Authors
  1. Eiji Miyoshi
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  2. Katsuhisa Noda
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  3. Naoyuki Taniguchi
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  4. Yutaka Sasaki
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  5. Norio Hayashi
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Editors and Affiliations

  1. First Department of Internal Medicine, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, 755-8505, Ube, Yamaguchi, Japan

    Kiwamu Okita M.D., Ph.D. (Professor and Chairman) (Professor and Chairman)

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© 2001 Springer-Verlag Tokyo

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Miyoshi, E., Noda, K., Taniguchi, N., Sasaki, Y., Hayashi, N. (2001). Significance of α1-6 Fucosylation in Hepatocellular Carcinoma. In: Okita, K. (eds) Liver Cirrhosis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68343-8_12

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  • DOI: https://doi.org/10.1007/978-4-431-68343-8_12

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68345-2

  • Online ISBN: 978-4-431-68343-8

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