Migrastatin analogues target fascin to block tumour metastasis

Lin Chen, Shengyu Yang, Jean Jakoncic, J. Jillian Zhang, Xin Yun Huang

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1062-1066
Number of pages5
JournalNature
Volume464
Issue number7291
DOIs
StatePublished - Apr 15 2010

All Science Journal Classification (ASJC) codes

  • General

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