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】
Free