News Story: Full Text
Sponsored By
Cedars-Siani Medical Center Brain Tumor Program
Please Click On The Above Banner For More Details
Braintumor Website

 

ADP-ribosylation factor 6 regulates glioma cell invasion through the IQ-domain GTPase-activating protein 1-Rac1-mediated pathway.


Posted on: 03/08/2009

Cancer Res. 2009 Feb 1;69(3):794-801. Epub 2009 Jan 20. 


ADP-ribosylation factor 6 regulates glioma cell invasion through the IQ-domain GTPase-activating protein 1-Rac1-mediated pathway.

 

Hu B, Shi B, Jarzynka MJ, Yiin JJ, D'Souza-Schorey C, Cheng SY.
Departments of Medicine and Pathology, Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. hub@upmc.edu

A common pathobiological feature of malignant gliomas is the insidious infiltration of single tumor cells into the brain parenchyma, rendering these deadly tumors virtually incurable with available therapies. In this study, we report that ADP-ribosylation factor 6 (ARF6), a Ras superfamily small GTPase, is abundantly expressed in invasive human glioma cells. Cellular depletion of ARF6 by small interfering RNA decreased Rac1 activation, impaired HGF-stimulated and serum-stimulated glioma cell migration in vitro, and markedly decreased the invasive capacity of invasive glioma in the brain. Furthermore, ectopic expression of ARF6 in glioma cells promoted cell migration via the activation of Rac1. Upon stimulation of glioma cells with HGF, we show that IQ-domain GTPase-activating protein 1 (IQGAP1) is recruited and overlaps with ARF6 at the leading edge of migrating cells. However, cellular depletion of ARF6 abrogated this recruitment of IQGAP1 and attenuated the formation of surface protrusions. ARF6 forms complexes with Rac1 and IQGAP1 in glioma cells upon HGF stimulation, and knockdown of IQGAP1 significantly inhibits ARF6-induced Rac1 activation and cell migration. Taken together, these data suggest that ARF6-mediated Rac1 activation is essential for glioma cell invasion via a signaling pathway that requires IQGAP1.

PMID: 19155310 [PubMed - in process]
PMCID: PMC2633432

 


Click HERE to return to brain tumor news headlines


Home | Brain Tumor Guide | FAQs | Find A Treatment
Noteworthy Treatments | News | Virtual Trial | Videos | Novocure Optune® | Newsletter
Donations | Brain Tumor Centers | Survivor Stories | Temodar®
Fundraising For Research | Unsubscribe | Contact Us

Copyright (c) 1993 - 2019 by:
The Musella Foundation For Brain Tumor Research & Information, Inc
1100 Peninsula Blvd
Hewlett, NY 11557
888-295-4740