GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:20393565

From GONUTS
Jump to: navigation, search
Citation

Chen, L, Yang, S, Jakoncic, J, Zhang, JJ and Huang, XY (2010) Migrastatin analogues target fascin to block tumour metastasis. Nature 464:1062-6

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.

Links

PubMed PMC2857318 Online version:10.1038/nature08978

Keywords

Actins/metabolism; Animals; Antineoplastic Agents/chemistry; Antineoplastic Agents/metabolism; Antineoplastic Agents/pharmacology; Antineoplastic Agents/therapeutic use; Binding Sites/drug effects; Breast Neoplasms/drug therapy; Breast Neoplasms/pathology; Carrier Proteins/antagonists & inhibitors; Carrier Proteins/chemistry; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Line, Tumor; Cell Movement/drug effects; Crystallography, X-Ray; Drug Resistance, Neoplasm/genetics; Female; Humans; Lung Neoplasms/prevention & control; Lung Neoplasms/secondary; Macrolides/chemistry; Macrolides/metabolism; Macrolides/pharmacology; Macrolides/therapeutic use; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Mice, SCID; Microfilament Proteins/antagonists & inhibitors; Microfilament Proteins/chemistry; Microfilament Proteins/genetics; Microfilament Proteins/metabolism; Models, Molecular; Mutation/genetics; Neoplasm Invasiveness/pathology; Neoplasm Invasiveness/prevention & control; Neoplasm Metastasis/drug therapy; Neoplasm Metastasis/pathology; Neoplasm Metastasis/prevention & control; Piperidones/chemistry; Piperidones/metabolism; Piperidones/pharmacology; Piperidones/therapeutic use; Protein Conformation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:FSCN1

enables

GO:0008144: drug binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:FSCN1

involved_in

GO:0016477: cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FSCN1

enables

GO:0003779: actin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:FSCN1

involved_in

GO:0051017: actin filament bundle assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FSCN1

enables

GO:0008144: drug binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FSCN1

involved_in

GO:0016477: cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:Q96IH1

enables

GO:0003779: actin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:Q96IH1

enables

GO:0008144: drug binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:Q96IH1

involved_in

GO:0016477: cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:Q96IH1

involved_in

GO:0051017: actin filament bundle assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.