title: The small GTPase RhoG mediates glioblastoma cell invasion.
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.
authors.affiliation: Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research at North Shore-LIJ, Manhasset, NY, USA.
authors.forename: Aneta
authors.initials: A
authors.lastname: Kwiatkowska
authors.forename: Sebastien
authors.initials: S
authors.lastname: Didier
authors.forename: Shannon
authors.initials: S
authors.lastname: Fortin
authors.forename: Yayu
authors.initials: Y
authors.lastname: Chuang
authors.forename: Timothy
authors.initials: T
authors.lastname: White
authors.forename: Michael E
authors.initials: ME
authors.lastname: Berens
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rushing
authors.forename: Jennifer
authors.initials: J
authors.lastname: Eschbacher
authors.forename: Nhan L
authors.initials: NL
authors.lastname: Tran
authors.forename: Amanda
authors.initials: A
authors.lastname: Chan
authors.forename: Marc
authors.initials: M
authors.lastname: Symons
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005909:Glioblastoma / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009479:Neuropeptides / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure; D011699:Putamen / Q000737:chemistry / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D009479:Neuropeptides; D034741:RNA, Small Interfering; C484602:Rac1 protein, mouse; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins