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

Cell Chem Biol. 2017 Dec 21;24(12):1467-1478.e5. doi: 10.1016/j.chembiol.2017.08.023. Epub 2017 Oct 12.


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.

Keywords: FX (TSTA3); fucose; fucosylation inhibitor; glycosylation; sugar analog.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Alkynes / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carbohydrate Epimerases / antagonists & inhibitors*
  • Carbohydrate Epimerases / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Fucose / chemistry
  • Fucose / pharmacology*
  • Guanosine Diphosphate Fucose / biosynthesis*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Ketone Oxidoreductases / antagonists & inhibitors*
  • Ketone Oxidoreductases / metabolism
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology


  • Alkynes
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Guanosine Diphosphate Fucose
  • Fucose
  • TSTA3 protein, human
  • Ketone Oxidoreductases
  • Carbohydrate Epimerases