The guanine nucleotide exchange factors Trio, Ect2, and Vav3 mediate the invasive behavior of glioblastoma

Bodour Salhia, Nhan L. Tran, Amanda Chan, Amparo Wolf, Mitsutoshi Nakada, Fiona Rutka, Matthew Ennis, Wendy S. McDonough, Michael E. Berens, Marc Symons, James T. Rutka

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

Malignant gliomas are characterized by their ability to invade normal brain tissue. We have previously shown that the small GTPase Rac1 plays a role in both migration and invasion in gliomas. Here, we aim to identify Rac-activating guanine nucleotide exchange factors (GEFs) that mediate glioblastoma invasiveness. Using a brain tumor expression database, we identified three GEFs, Trio, Ect2, and Vav3, that are expressed at higher levels in glioblastoma versus low-grade glioma. The expression of these GEFs is also associated with poor patient survival. Quantitative real-time polymerase chain reaction and immunohistochemical analyses on an independent set of tumors confirmed that these GEFs are overexpressed in glioblastoma as compared with either nonneoplastic brain or low-grade gliomas. In addition, depletion of Trio, Ect2, and Vav3 by siRNA oligonucleotides suppresses glioblastoma cell migration and invasion. Depletion of either Ect2 or Trio also reduces the rate of cell proliferation. These results suggest that targeting GEFs may present novel strategies for anti-invasive therapy for malignant gliomas.

Original languageEnglish (US)
Pages (from-to)1828-1838
Number of pages11
JournalAmerican Journal of Pathology
Volume173
Issue number6
DOIs
StatePublished - Dec 2008

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Salhia, B., Tran, N. L., Chan, A., Wolf, A., Nakada, M., Rutka, F., Ennis, M., McDonough, W. S., Berens, M. E., Symons, M., & Rutka, J. T. (2008). The guanine nucleotide exchange factors Trio, Ect2, and Vav3 mediate the invasive behavior of glioblastoma. American Journal of Pathology, 173(6), 1828-1838. https://doi.org/10.2353/ajpath.2008.080043