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

Research output: Contribution to journalArticle

13 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

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GDPmannose 4,6-dehydratase
Guanosine Diphosphate Fucose
Fucose
Cell Movement
Hepatocellular Carcinoma
Polysaccharides
Alkynes
Inflammation
Ligases

All Science Journal Classification (ASJC) codes

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

Cite this

Kizuka, Yasuhiko ; Nakano, Miyako ; Yamaguchi, Yoshiki ; Nakajima, Kazuki ; Oka, Ritsuko ; Sato, Keiko ; Ren, Chien Tai ; Hsu, Tsui Ling ; Wong, Chi Huey ; Taniguchi, Naoyuki. / An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP-Fucose-Synthesizing Enzyme FX, TSTA3. In: Cell Chemical Biology. 2017 ; Vol. 24, No. 12. pp. 1467-1478.e5.
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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.",
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Kizuka, Y, Nakano, M, Yamaguchi, Y, Nakajima, K, Oka, R, Sato, K, Ren, CT, Hsu, TL, Wong, CH & Taniguchi, N 2017, 'An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP-Fucose-Synthesizing Enzyme FX, TSTA3', Cell Chemical Biology, vol. 24, no. 12, pp. 1467-1478.e5. https://doi.org/10.1016/j.chembiol.2017.08.023

An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP-Fucose-Synthesizing Enzyme FX, TSTA3. / Kizuka, Yasuhiko; Nakano, Miyako; Yamaguchi, Yoshiki; Nakajima, Kazuki; Oka, Ritsuko; Sato, Keiko; Ren, Chien Tai; Hsu, Tsui Ling; Wong, Chi Huey; Taniguchi, Naoyuki.

In: Cell Chemical Biology, Vol. 24, No. 12, 21.12.2017, p. 1467-1478.e5.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP-Fucose-Synthesizing Enzyme FX, TSTA3

AU - Kizuka, Yasuhiko

AU - Nakano, Miyako

AU - Yamaguchi, Yoshiki

AU - Nakajima, Kazuki

AU - Oka, Ritsuko

AU - Sato, Keiko

AU - Ren, Chien Tai

AU - Hsu, Tsui Ling

AU - Wong, Chi Huey

AU - Taniguchi, Naoyuki

PY - 2017/12/21

Y1 - 2017/12/21

N2 - 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.

AB - 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.

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