論文 - 詳細
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 | 2017-12-21 |
DOI | 10.1016/j.chembiol.2017.08.023 |
PII | S2451-9456(17)30321-5 |
PMID | 29033318 |
MeSH | 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 |
IF | 6.762 |
引用数 | 13 |
リソース情報 | |
ヒト・動物細胞 | COS-7(RCB0539) |