The small GTPase RhoG mediates glioblastoma cell invasion

Molecular Cancer

Research

Jennifer Eschbacher¹  Nhan L Tran²  Michael E Berens²  Shannon Fortin³  Amanda Chan⁴  Sebastien Didier⁴  Timothy White⁴  Aneta Kwiatkowska⁴  Yayu Chuang⁴  Marc Symons⁵  Elisabeth Rushing⁶ 

[1] Barrow Neurological Institute, Phoenix, AZ, USA;Cancer and Cell Biology Division, The Translational Genomics Research Institute, Phoenix, AZ, USA;Cancer and Cell Biology Division, The Translational Genomics Research Institute, Phoenix, AZ, USA;Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ, USA;Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research at North Shore-LIJ, Manhasset, NY, USA;Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research at North Shore-LIJ, Manhasset, NY, USA;Departments of Molecular Medicine and Neurosurgery, Hofstra-North Shore LIJ School of Medicine, Hempstead, NY, USA;The Feinstein Institute for Medical Research, 350 Community Dr, 11030, Manhasset, NY, USA;UniversitätsSpital Zürich, Zürich, Switzerland;

关键词: RhoG;    Rac1;    cMet;    EGFR;    Glioblastoma;    Invasion;   

DOI  :  10.1186/1476-4598-11-65

 received in 2012-02-07, accepted in 2012-07-18,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe invasion of glioblastoma cells into regions of the normal brain is a critical factor that limits current therapies for malignant astrocytomas. Previous work has identified roles for the Rho family guanine nucleotide exchange factors Trio and Vav3 in glioblastoma invasion. Both Trio and Vav3 act on the small GTPase RhoG. We therefore examined the role of RhoG in the invasive behavior of glioblastoma cells.ResultsWe found that siRNA-mediated depletion of RhoG strongly inhibits invasion of glioblastoma cells through brain slices ex vivo. In addition, depletion of RhoG has a marginal effect on glioblastoma cell proliferation, but significantly inhibits glioblastoma cell survival in colony formation assays. We also observed that RhoG is activated by both HGF and EGF, two factors that are thought to be clinically relevant drivers of glioblastoma invasive behavior, and that RhoG is overexpressed in human glioblastoma tumors versus non-neoplastic brain. In search of a mechanism for the contribution of RhoG to the malignant behavior of glioblastoma cells, we found that depletion of RhoG strongly inhibits activation of the Rac1 GTPase by both HGF and EGF. In line with this observation, we also show that RhoG contributes to the formation of lamellipodia and invadopodia, two functions that have been shown to be Rac1-dependent.ConclusionsOur functional analysis of RhoG in the context of glioblastoma revealed a critical role for RhoG in tumor cell invasion and survival. These results suggest that targeting RhoG-mediated signaling presents a novel avenue for glioblastoma therapy.

【 授权许可】

Unknown   
© Kwiatkowska et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.