Migrastatin analogues target fascin to block tumour metastasis

被引：229

作者：

Chen, Lin ^{[1
]}

Yang, Shengyu ^{[1
]}

Jakoncic, Jean ^{[2
]}

Zhang, J. Jillian ^{[1
]}

Huang, Xin-Yun ^{[1
]}

机构：

[1] Cornell Univ, Weill Med Coll, Dept Physiol, New York, NY 10065 USA

[2] Brookhaven Natl Lab, Natl Synchrotron Light Source, Upton, NY 11973 USA

来源：

NATURE | 2010年 / 464卷 / 7291期

基金：

美国国家卫生研究院;

关键词：

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

D O I：

10.1038/nature08978

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页码：1062 / U135

页数：7

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