Tumoral migration and invasion RECK-mediated: melanoma as a model
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|Support Opportunities:||Scholarships in Brazil - Master|
|Effective date (Start):||March 01, 2010|
|Effective date (End):||May 31, 2012|
|Field of knowledge:||Biological Sciences - Morphology - Cytology and Cell Biology|
|Principal Investigator:||Silvya Stuchi Maria-Engler|
|Grantee:||Raquel Brandão Haga|
|Host Institution:||Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil|
Gliomas are highly invasive, treatment-resistant and lethal tumors. Overexpression of RECK in human glioma cell line T98G decreased cell migration and invasion in vitro, lead to cytoskeleton rearrangement and caused changes in phospho-FAK distribution. However, the pathway involved in RECK-mediated inhibition of cell migration has not been elucidated yet. To study the mechanisms by which RECK affects cell motility, T98G cells were transfected with pCXN2-hRECK vector (RECK+). Some proteins involved in the integrin pathway, activity of some proteins of RhoGTPase family and cytoskeleton proteins were analyzed through immunoblotting, immunostaining and pull-down assay in RECK+ cells and compared with non-transfected T98G cells, T98G transfected with pCXN2 without RECK gene and human primary fibroblasts (FF287). Our results showed an increase in integrin ²1 expression and a decrease in FAK phosphorylation in the Tyr397 site, which together with the increase of stress fibers and decrease of lamellipodia, suggest a less migratory phenotype. Despite this, Rac1 activity was increased even though one of Rac activation pathways is through phospho-FAK, leading to lamellipodium formation. Our hypotheses is that RECK affects focal adhesion turnover, diminishing cell motility. As cells are still receiving a positive signal to migrate, they activate Rac1 through a FAK-independent pathway. Besides that, paxillin immunostaining showed that focal adhesions are larger in RECK+ cells, indicating that RECK can influence structures related with cell-matrix contact.
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