Migrastatin analogues target fascin to block tumour metastasis

Article

关键词: CELL-MIGRATION INHIBITORS;    NEGATIVE BREAST-CANCER;    ACTIN-BUNDLING PROTEIN;    EXPRESSION;    CARCINOMA;    MOTILITY;    GENE;    DISCOVERY;    FILOPODIA;    ROLES;   

DOI  :  10.1038/nature08978

来源: SCIE

【 摘 要 】

Tumour metastasis is the primary cause of death of cancer patients. Development of new therapeutics preventing tumour metastasis is urgently needed. Migrastatin is a natural product secreted by Streptomyces(1,2), and synthesized migrastatin analogues such as macroketone are potent inhibitors of metastatic tumour cell migration, invasion and metastasis(3-6). Here we show that these migrastatin analogues target the actin-bundling protein fascin to inhibit its activity. X-ray crystal structural studies reveal that migrastatin analogues bind to one of the actin-binding sites on fascin. Our data demonstrate that actin cytoskeletal proteins such as fascin can be explored as new molecular targets for cancer treatment, in a similar manner to the microtubule protein tubulin.

【 授权许可】

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