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*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Title of host publicationSignaling Pathways and Molecular Mediators in Metastasis
PublisherSpringer Netherlands
Pages143-169
Number of pages27
ISBN (Electronic)9789400725584
ISBN (Print)9400725574, 9789400725577
DOIs
StatePublished - Jan 1 2014

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GTP Phosphohydrolase Activators
Guanine Nucleotide Exchange Factors
rho GTP-Binding Proteins
Glioblastoma
Glioma
Neoplasms
Brain Neoplasms
Cell Movement
Membrane Proteins
Neoplasm Metastasis
Phenotype
Mutation
Brain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hu, B., Symons, M., Salhia, B., Fortin, S. P., Tran, N. L., Rutka, J., & Cheng, S. Y. (2014). Rho GTPases and their activators, guanine nucleotide exchange factors (GEFs): Their roles in glioma cell invasion. In Signaling Pathways and Molecular Mediators in Metastasis (pp. 143-169). Springer Netherlands. https://doi.org/10.1007/978-94-007-2558-4_6
Hu, Bo ; Symons, Marc ; Salhia, Bodour ; Fortin, Shannon P. ; Tran, Nhan L. ; Rutka, James ; Cheng, Shi Yuan. / Rho GTPases and their activators, guanine nucleotide exchange factors (GEFs) : Their roles in glioma cell invasion. Signaling Pathways and Molecular Mediators in Metastasis. Springer Netherlands, 2014. pp. 143-169
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abstract = "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.",
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Hu, B, Symons, M, Salhia, B, Fortin, SP, Tran, NL, Rutka, J & Cheng, SY 2014, Rho GTPases and their activators, guanine nucleotide exchange factors (GEFs): Their roles in glioma cell invasion. in Signaling Pathways and Molecular Mediators in Metastasis. Springer Netherlands, pp. 143-169. https://doi.org/10.1007/978-94-007-2558-4_6

Rho GTPases and their activators, guanine nucleotide exchange factors (GEFs) : Their roles in glioma cell invasion. / Hu, Bo; Symons, Marc; Salhia, Bodour; Fortin, Shannon P.; Tran, Nhan L.; Rutka, James; Cheng, Shi Yuan.

Signaling Pathways and Molecular Mediators in Metastasis. Springer Netherlands, 2014. p. 143-169.

Research output: Chapter in Book/Report/Conference proceedingChapter

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AU - Rutka, James

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AB - 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.

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Hu B, Symons M, Salhia B, Fortin SP, Tran NL, Rutka J et al. Rho GTPases and their activators, guanine nucleotide exchange factors (GEFs): Their roles in glioma cell invasion. In Signaling Pathways and Molecular Mediators in Metastasis. Springer Netherlands. 2014. p. 143-169 https://doi.org/10.1007/978-94-007-2558-4_6