Document Details

Document Type : Article In Journal 
Document Title :
Involvement of the RASSF1A Tumor Suppressor Gene in Controlling Cell Migration
Involvement of the RASSF1A Tumor Suppressor Gene in Controlling Cell Migration
 
Document Language : English 
Abstract : 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 cellcell adhesion and a more refractive morphology. RASSF1Adepleted 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 fibroblastlike 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 RASSF1Aknockdown 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. 
ISSN : 1538-7445 
Journal Name : CANCER RESEARCH 
Volume : 65 
Issue Number : 17 
Publishing Year : 1426 AH
2005 AD 
Article Type : Article 
Added Date : Monday, April 26, 2010 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
فريدة لطيفLatif, Farida InvestigatorDoctorateflatif@hgmp.mrc.ac.uk
أشرف دلولDallol, Ashraf ResearcherDoctorate 

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