An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP-Fucose-Synthesizing Enzyme FX, TSTA3
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), w...
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Published in | Cell chemical biology Vol. 24; no. 12; pp. 1467 - 1478.e5 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Ltd
21.12.2017
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Subjects | |
Online Access | Get full text |
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Summary: | 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.
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•6-Alkynyl-fucose, a widely used fucosylation probe, strongly inhibits fucosylation•6-Alkynyl-fucose competitively inhibits GDP-fucose synthetase FX•6-Alkynyl-fucose halts hepatoma invasion•6-Alkynyl-fucose is a powerful tool for modulating cellular fucosylation
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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ISSN: | 2451-9456 2451-9448 2451-9456 |
DOI: | 10.1016/j.chembiol.2017.08.023 |