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Nature. 2010 Apr 15;464(7291):1062-6. doi: 10.1038/nature08978.

Migrastatin analogues target fascin to block tumour metastasis.

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  • 1Department of Physiology, Cornell University Weill Medical College, New York, New York 10065, USA.

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  • Nature. 2011 Aug 11;476(7359):240.

Abstract

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, and synthesized migrastatin analogues such as macroketone are potent inhibitors of metastatic tumour cell migration, invasion and metastasis. 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.

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PMID:
20393565
[PubMed - indexed for MEDLINE]
PMCID:
PMC2857318
Free PMC Article

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