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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Molecular Cancer 1/2012

The small GTPase RhoG mediates glioblastoma cell invasion

Molecular Cancer > Ausgabe 1/2012
Aneta Kwiatkowska, Sebastien Didier, Shannon Fortin, Yayu Chuang, Timothy White, Michael E Berens, Elisabeth Rushing, Jennifer Eschbacher, Nhan L Tran, Amanda Chan, Marc Symons
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1476-4598-11-65) contains supplementary material, which is available to authorized users.
Aneta Kwiatkowska, Sebastien Didier contributed equally to this work.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

AK performed the cell proliferation, in vitro invasion and lamellipodia formation studies and participated in the Rac activation assays. SD performed the RhoG and Rac activation studies and part of the colony formation assays. SF performed the brain slice invasion assay. YC performed the invadopodia formation assay. TW performed part of the colony formation assays. MEB provided the TMA slides and ER and JE interpreted and scored the TMA assays. NT supervised and coordinated performance of the brain slice assay and IHC staining. AC participated in the design of the study, implemented the RhoG activation assay and produced preliminary data for most of the functional assays. MS designed and coordinated the overall study and drafted the manuscript. All authors read and approved the final manuscript.



The 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.


We 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.


Our 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.
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