The small GTPase RhoG mediates glioblastoma cell invasion

Persistent Link:
http://hdl.handle.net/10150/610207
Title:
The small GTPase RhoG mediates glioblastoma cell invasion
Author:
Kwiatkowska, Aneta; Didier, Sebastien; Fortin, Shannon; Chuang, Yayu; White, Timothy; Berens, Michael; Rushing, Elisabeth; Eschbacher, Jennifer; Tran, Nhan; Chan, Amanda; Symons, Marc
Affiliation:
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; Cancer and Cell Biology Division, The Translational Genomics Research Institute, Phoenix, AZ, USA; Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ, USA; UniversitätsSpital Zürich, Zürich, Switzerland; Barrow Neurological Institute, Phoenix, AZ, USA; The Feinstein Institute for Medical Research 350 Community Dr, Manhasset, NY, 11030, USA
Issue Date:
2012
Publisher:
BioMed Central
Citation:
Kwiatkowska et al. Molecular Cancer 2012, 11:65 http://www.molecular-cancer.com/content/11/1/65
Journal:
Molecular Cancer
Rights:
© 2012 Kwiatkowska et al.; licensee 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)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND: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.RESULTS: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.CONCLUSIONS: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.
EISSN:
1476-4598
DOI:
10.1186/1476-4598-11-65
Keywords:
RhoG; Rac1; cMet; EGFR; Glioblastoma; Invasion
Version:
Final published version
Additional Links:
http://www.molecular-cancer.com/content/11/1/65

Full metadata record

DC FieldValue Language
dc.contributor.authorKwiatkowska, Anetaen
dc.contributor.authorDidier, Sebastienen
dc.contributor.authorFortin, Shannonen
dc.contributor.authorChuang, Yayuen
dc.contributor.authorWhite, Timothyen
dc.contributor.authorBerens, Michaelen
dc.contributor.authorRushing, Elisabethen
dc.contributor.authorEschbacher, Jenniferen
dc.contributor.authorTran, Nhanen
dc.contributor.authorChan, Amandaen
dc.contributor.authorSymons, Marcen
dc.date.accessioned2016-05-20T09:01:06Z-
dc.date.available2016-05-20T09:01:06Z-
dc.date.issued2012en
dc.identifier.citationKwiatkowska et al. Molecular Cancer 2012, 11:65 http://www.molecular-cancer.com/content/11/1/65en
dc.identifier.doi10.1186/1476-4598-11-65en
dc.identifier.urihttp://hdl.handle.net/10150/610207-
dc.description.abstractBACKGROUND: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.RESULTS: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.CONCLUSIONS: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.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.molecular-cancer.com/content/11/1/65en
dc.rights© 2012 Kwiatkowska et al.; licensee 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)en
dc.subjectRhoGen
dc.subjectRac1en
dc.subjectcMeten
dc.subjectEGFRen
dc.subjectGlioblastomaen
dc.subjectInvasionen
dc.titleThe small GTPase RhoG mediates glioblastoma cell invasionen
dc.typeArticleen
dc.identifier.eissn1476-4598en
dc.contributor.departmentCenter for Oncology and Cell Biology, The Feinstein Institute for Medical Research at North Shore-LIJ, Manhasset, NY, USAen
dc.contributor.departmentDepartments of Molecular Medicine and Neurosurgery, Hofstra-North Shore LIJ School of Medicine, Hempstead, NY, USAen
dc.contributor.departmentCancer and Cell Biology Division, The Translational Genomics Research Institute, Phoenix, AZ, USAen
dc.contributor.departmentCancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ, USAen
dc.contributor.departmentUniversitätsSpital Zürich, Zürich, Switzerlanden
dc.contributor.departmentBarrow Neurological Institute, Phoenix, AZ, USAen
dc.contributor.departmentThe Feinstein Institute for Medical Research 350 Community Dr, Manhasset, NY, 11030, USAen
dc.identifier.journalMolecular Canceren
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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