Document Detail


Involvement of adaptor protein Crk in malignant feature of human ovarian cancer cell line MCAS.
MedLine Citation:
PMID:  16491127     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Signaling adaptor protein Crk regulates cell motility and growth through its targets Dock180 and C3G, those are the guanine-nucleotide exchange factors (GEFs) for small GTPases Rac and Rap, respectively. Recently, overexpression of Crk has been reported in various human cancers. To define the role for Crk in human cancer cells, Crk expression was targeted in the human ovarian cancer cell line MCAS through RNA interference, resulting in the establishment of three Crk knockdown cell lines. These cell lines exhibited disorganized actin fibers, reduced number of focal adhesions, and abolishment of lamellipodia formation. Decreased Rac activity was demonstrated by pull-down assay and FRET-based time-lapse microscopy, in association with suppression of both motility and invasion by phagokinetic track assay and transwell assay in these cells. Furthermore, Crk knockdown cells exhibited slow growth rates in culture and suppressed anchorage-dependent growth in soft agar. Tumor forming potential in nude mice was attenuated, and intraperitoneal dissemination was not observed when Crk knockdown cells were injected into the peritoneal cavity. These results suggest that the Crk is a key component of focal adhesion and involved in cell growth, invasion, and dissemination of human ovarian cancer cell line MCAS.
Authors:
H Linghu; M Tsuda; Y Makino; M Sakai; T Watanabe; S Ichihara; H Sawa; K Nagashima; N Mochizuki; S Tanaka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-02-20
Journal Detail:
Title:  Oncogene     Volume:  25     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-15     Completed Date:  2006-08-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  3547-56     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Adhesion / physiology
Cell Line, Tumor
Cell Proliferation
Female
Fluorescent Antibody Technique
Humans
Immunoblotting
Mice
Mice, Nude
Microfilaments / pathology
Neoplasm Invasiveness*
Neoplasms, Experimental / metabolism,  pathology
Ovarian Neoplasms / metabolism*,  pathology
Proto-Oncogene Proteins c-crk / metabolism*
Pseudopodia / pathology
RNA Interference
rac GTP-Binding Proteins / metabolism
Chemical
Reg. No./Substance:
0/CRK protein, human; 0/Proto-Oncogene Proteins c-crk; EC 3.6.5.2/rac GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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