An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP-Fucose-Synthesizing Enzyme FX, TSTA3

Yasuhiko Kizuka, Miyako Nakano, Yoshiki Yamaguchi, Kazuki Nakajima, Ritsuko Oka, Keiko Sato, Chien Tai Ren, Tsui Ling Hsu, Chi Huey Wong, Naoyuki Taniguchi

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    56 Citations (Scopus)

    Abstract

    Fucosylation is a glycan modification critically involved in cancer and inflammation. Although potent fucosylation inhibitors are useful for basic and clinical research, only a few inhibitors have been developed. Here, we focus on a fucose analog with an alkyne group, 6-alkynyl-fucose (6-Alk-Fuc), which is used widely as a detection probe for fucosylated glycans, but is also suggested for use as a fucosylation inhibitor. Our glycan analysis using lectin and mass spectrometry demonstrated that 6-Alk-Fuc is a potent and general inhibitor of cellular fucosylation, with much higher potency than the existing inhibitor, 2-fluoro-fucose (2-F-Fuc). The action mechanism was shown to deplete cellular GDP-Fuc, and the direct target of 6-Alk-Fuc is FX (encoded by TSTA3), the bifunctional GDP-Fuc synthase. We also show that 6-Alk-Fuc halts hepatoma invasion. These results highlight the unappreciated role of 6-Alk-Fuc as a fucosylation inhibitor and its potential use for basic and clinical science. Fucose sugar is involved in cancer and inflammation. Kizuka et al. found that a fucose alkyne strongly inhibits cellular fucosylation. The compound selectively inhibits GDP-fucose synthetase FX and can be applied to glycan-related diseases.

    Original languageEnglish
    Pages (from-to)1467-1478.e5
    JournalCell Chemical Biology
    Volume24
    Issue number12
    DOIs
    Publication statusPublished - 21-12-2017

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Pharmacology
    • Drug Discovery
    • Clinical Biochemistry

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