The Guanine Nucleotide Exchange Factors Trio, Ect2, and Vav3 Mediate the Invasive Behavior of Glioblastoma

被引：144

作者：

Salhia, Bodour ^{[1
,2
]}

Tran, Nhan L. ^{[2
]}

Chan, Amanda ^{[3
]}

Wolf, Amparo ^{[1
]}

Nakada, Mitsutoshi ^{[4
]}

Rutka, Fiona ^{[1
]}

Ennis, Matthew ^{[2
]}

McDonough, Wendy S. ^{[2
]}

Berens, Michael E. ^{[2
]}

Symons, Marc ^{[3
]}

Rutka, James T. ^{[1
]}

机构：

[1] Univ Toronto, Hosp Sick Children, Canc & Cell Biol Div, Arthur & Sonia Labatt Brain Tumor Res Ctr, Toronto, ON M5G 1X8, Canada

[2] Translat Genom Res Inst, Phoenix, AZ USA

[3] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Dept Canc & Cell Biol, Manhasset, NY USA

[4] Kanazawa Univ, Grad Sch Med, Div Neurosurg, Kanazawa, Ishikawa, Japan

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2008年 / 173卷 / 06期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

D O I：

10.2353/ajpath.2008.080043

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

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. (Am J Pathol 2008, 173:1828-1838; DOI: 10.2353/ajpath.2008.080043; DOI: 10.2353/ajpath.2008.080043)

引用

页码：1828 / 1838

页数：11

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