TY - CHAP
T1 - Rho GTPases and their activators, guanine nucleotide exchange factors (GEFs)
T2 - Their roles in glioma cell invasion
AU - Hu, Bo
AU - Symons, Marc
AU - Salhia, Bodour
AU - Fortin, Shannon P.
AU - Tran, Nhan L.
AU - Rutka, James
AU - Cheng, Shi Yuan
N1 - Publisher Copyright:
© 2012 Springer Science+Business Media B.V. All rights reserved.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
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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U2 - 10.1007/978-94-007-2558-4_6
DO - 10.1007/978-94-007-2558-4_6
M3 - Chapter
AN - SCOPUS:84908303348
SN - 9400725574
SN - 9789400725577
SP - 143
EP - 169
BT - Signaling Pathways and Molecular Mediators in Metastasis
PB - Springer Netherlands
ER -