RRC ID 49612
著者 Kizuka Y, Nakano M, Yamaguchi Y, Nakajima K, Oka R, Sato K, Ren CT, Hsu TL, Wong CH, Taniguchi N.
タイトル An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP-Fucose-Synthesizing Enzyme FX, TSTA3.
ジャーナル Cell Chem Biol
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.
巻・号 24(12)
ページ 1467-1478.e5
公開日 2017-10-17
DOI 10.1016/j.chembiol.2017.08.023
PII S2451-9456(17)30321-5
PMID 29033318
ヒト・動物細胞 COS-7(RCB0539)