Publication Date:
2010-04-16
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857318/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857318/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Lin -- Yang, Shengyu -- Jakoncic, Jean -- Zhang, J Jillian -- Huang, Xin-Yun -- CA136837/CA/NCI NIH HHS/ -- R01 CA136837/CA/NCI NIH HHS/ -- R01 CA136837-01A1/CA/NCI NIH HHS/ -- England -- Nature. 2010 Apr 15;464(7291):1062-6. doi: 10.1038/nature08978.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Cornell University Weill Medical College, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393565" target="_blank"〉PubMed〈/a〉
Keywords:
Actins/metabolism
;
Animals
;
Antineoplastic Agents/chemistry/metabolism/pharmacology/therapeutic use
;
Binding Sites/drug effects
;
Breast Neoplasms/drug therapy/pathology
;
Carrier Proteins/*antagonists & inhibitors/chemistry/genetics/metabolism
;
Cell Line, Tumor
;
Cell Movement/drug effects
;
Crystallography, X-Ray
;
Drug Resistance, Neoplasm/genetics
;
Female
;
Humans
;
Lung Neoplasms/prevention & control/secondary
;
Macrolides/*chemistry/metabolism/*pharmacology/therapeutic use
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred NOD
;
Mice, SCID
;
Microfilament Proteins/*antagonists & inhibitors/chemistry/genetics/metabolism
;
Models, Molecular
;
Mutation/genetics
;
Neoplasm Invasiveness/pathology/prevention & control
;
Neoplasm Metastasis/drug therapy/pathology/*prevention & control
;
Piperidones/*chemistry/metabolism/*pharmacology/therapeutic use
;
Protein Conformation
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
