Document Detail

Involvement of the RASSF1A tumor suppressor gene in controlling cell migration.
MedLine Citation:
PMID:  16140931     Owner:  NLM     Status:  MEDLINE    
We have previously shown that RASSF1A associates with the microtubules. This association alters the microtubule dynamics and seems essential for RASSF1A tumor suppressive function. Mutant variants of RASSF1A that do not associate fully with the microtubules have reduced ability to stabilize them and cause cell cycle arrest. Here we show that overexpression of RASSF1A diminished the ability of A549 non-small cell lung cancer cells to migrate either through a transwell filter or to close a wound. In addition, we employed gene knockdown as well as mouse embryonic fibroblasts (MEFs) from Rassf1a knockout mice to analyze RASSF1A function in controlling cell motility. A549 cells stably transfected with RASSF1A exhibited increased cell-cell adhesion and less refractive morphology compared with controls. Conversely, RASSF1A knockdown in HeLa caused loss of cell-cell adhesion and a more refractive morphology. RASSF1A-depleted HeLa cells as well as Rassf1a-/- MEFs displayed increased cell migration that could be partly phosphatidylinositol 3-kinase dependent. Time-lapse microscopy showed the RASSF1A-depleted cells are highly motile with fibroblast-like morphology and diminished cell-cell adhesion. Staining of the cytoskeleton in RASSF1A-depleted HeLa cells and MEFs show marked differences in terms of microtubules outgrowth and actin stress fibers formation. This observation was associated with increased activation of Rac1 in RASSF1A-knockdown cells and the Rassf1a-/- MEFs. In addition, expression of a dominant-negative variant of Rac1 in the RASSF1A-depleted HeLa cells reduced their ability to form lamellipodia and other protrusions. These findings represent a novel function for RASSF1A, which may help explain its tumor suppression ability independently of its effects on cell cycle and apoptosis.
Ashraf Dallol; Angelo Agathanggelou; Stella Tommasi; Gerd P Pfeifer; Eamonn R Maher; Farida Latif
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  65     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-05     Completed Date:  2005-11-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7653-9     Citation Subset:  IM    
Section of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
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MeSH Terms
Carcinoma, Non-Small-Cell Lung / genetics*,  metabolism,  pathology*
Cell Adhesion / genetics
Cell Line, Tumor
Cell Movement / genetics*
Cytoskeleton / metabolism
Genes, Tumor Suppressor / physiology
Hela Cells
Lung Neoplasms / genetics*,  metabolism,  pathology*
Microtubules / metabolism
Tumor Suppressor Proteins / biosynthesis,  genetics*
Reg. No./Substance:
0/RASSF1 protein, human; 0/Tumor Suppressor Proteins

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

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