Rho GTPases and Their Activators, Guanine Nucleotide Exchange Factors (GEFs): Their Roles in Glioma Cell Invasion

  • Bo Hu
  • Marc Symons
  • Bodour Salhia
  • Shannon P. Fortin
  • Nhan L. Tran
  • James Rutka
  • Shi-Yuan Cheng


Accumulated studies showed that constitutively activated Rho GTPases such as Rac1 in malignant human glioblastomas are responsible for the highly invasive phenotype observed in these aggressive brain cancers. Notably, no activating mutations of Rac1 have been reported in human glioblastomas or other types of cancers. Moreover, Rac1 and several GEFs have been implicated in cell invasion and metastasis of glioblastomas and other types of human cancers. Mechanistically, the functions of the Rho GTPases are regulated by three distinct classes of molecules. Among them, guanine nucleotide exchange factors (GEFs) are the activators for Rho GTPases. Here, we review the role of Rho GTPases, particularly Rac1 and several GEFs including Trio, SWAP-70, Ect2, Vav3 and Dock180-ELMO1 in ­glioblastoma cell invasion. Since studies of Rho GTPases and their GEFs in ­glioblastomas are just emerging, we place specific emphasis on the current knowledge of their roles in cell motility and cancer cell invasion as well as potential response to extracellular stimuli that promotes glioma cell invasion. Additionally, we include studies of two membrane receptor proteins, Fn14 and TROY that promote glioma cell invasion through activation of Rho GTPases. Lastly, we discuss future directions for understanding the functions of Rac1 and GEFs in glioma cell invasion and implications to establish these key modulators as potential targets to inhibit diffusely invasive glioblastomas in the brain. The insight provided by this review will help to develop new therapeutic approaches to treat patients with ­malignant gliomas.


Glioma Cell Anaplastic Large Cell Lymphoma Rac1 Activation Tumor Necrosis Factor Receptor Superfamily Glioma Cell Migration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Brain-specific angiogenesis inhibitor-1


v-crk sarcoma virus CT10 oncogene homolog


Diffuse B-cell lypmphoma


Death domain

DH domain

Dbl homology (DH) domain

DHR domain

Dock-homology region


Dedicator of cytokinesis


Epithelial cell transforming sequence 2


Epithelial growth factor receptor


Engulfment and cell motility-1


Fibroblast growth factor inducible 14


GTPase-activating protein


Glioblastoma multiforme


Guanine nucleotide dissociation inhibitor


Guanine nucleotide exchange factor (GDP–GTP exchange factor)


crk-associate substrate 130 kDa protein


Platelet-derived growth factor receptor

PH domain

Pleckstrin homology domain




proline-rich tyrosine kinase


RNA interference


Rho kinase

SH2 or 3

src homologous domain 2 or 3


switching B-cell complex 70 kDa subunit


Tumor necrosis factor


Tumor necrosis factor receptor superfamily


Tumor necrosis factor receptor associated factor


Triple function domains (PTPRF interacting)


Tumor necrosis factor receptor superfamily member 19


Triple sex combs


Tumor necrosis factor-like weak inducer of apoptosis


vav 3 guanine nucleotide exchange factor


Vascular endothelial growth factor receptor


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Bo Hu
    • 1
    • 2
  • Marc Symons
    • 3
  • Bodour Salhia
    • 4
  • Shannon P. Fortin
    • 4
  • Nhan L. Tran
    • 4
  • James Rutka
    • 5
  • Shi-Yuan Cheng
    • 1
    • 6
  1. 1.Cancer InstituteUniversity of Pittsburgh, School of MedicinePittsburghUSA
  2. 2.Department of MedicineUniversity of Pittsburgh, School of MedicinePittsburghUSA
  3. 3.Center for Oncology and Cell BiologyThe Feinstein Institute for Medical Research at North Shore-LIJManhassetUSA
  4. 4.Translational Genomics Research InstitutePhoenixUSA
  5. 5.The Arthur and Sonia Labatt Brain Tumor Research CenterHospital for Sick ChildrenTorontoCanada
  6. 6.Department of PathologyUniversity of Pittsburgh, School of MedicinePittsburghUSA

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