c-Src and Neural Wiskott-Aldrich Syndrome Protein N-WASP Promote Low Oxygen-Induced Accelerated Brain Invasion by GliomasReportar como inadecuado




c-Src and Neural Wiskott-Aldrich Syndrome Protein N-WASP Promote Low Oxygen-Induced Accelerated Brain Invasion by Gliomas - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Malignant gliomas remain associated with poor prognosis and high morbidity because of their ability to invade the brain; furthermore, human gliomas exhibit a phenotype of accelerated brain invasion in response to anti-angiogenic drugs. Here, we study 8 human glioblastoma cell lines; U251, U87, D54 and LN229 show accelerated motility in low ambient oxygen. Src inhibition by Dasatinib abrogates this phenotype. Molecular discovery and validation studies evaluate 46 molecules related to motility or the src pathway in U251 cells. Demanding that the molecular changes induced by low ambient oxygen are reversed by Dasatinib in U251 cells, identifies neural Wiskott-Aldrich syndrome protein NWASP, Focal adhesion Kinase FAK -Catenin, and Cofilin. However, only Src-mediated NWASP phosphorylation distinguishes the four cell lines that exhibit enhanced motility in low ambient oxygen. Downregulating c-Src or NWASP by RNA interference abrogates the low-oxygen-induced enhancement in motility by in vitro assays and in organotypic brain slice cultures. The findings support the idea that c-Src and NWASP play key roles in mediating the molecular pathogenesis of low oxygen-induced accelerated brain invasion by gliomas.



Autor: Zhuo Tang, Lita M. Araysi, Hassan M Fathallah-Shaykh

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados