Journal
CELLULAR SIGNALLING
Volume 23, Issue 6, Pages 969-979Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2010.10.022
Keywords
Vav1; Cytoskeleton; Rac; GEF; RhoGTPases
Categories
Funding
- Israel Academy of Sciences
- Israel Cancer Research Foundation
- Israeli Cancer Association
- Hubert H. Humphrey Center for Experimental Medicine and Cancer Research
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Rho guanosine triphosphatases (GTPases) are a family of small proteins which function as molecular switches in a variety of signaling pathways following stimulation of cell surface receptors. RhoGTPases regulate numerous cellular processes including cytoskeleton organization, gene transcription, cell proliferation, migration, growth and cell survival. Because of their central role in regulating processes that are dysregulated in cancer, it seems reasonable that defects in the RhoGTPase pathway may be involved in the development of cancer. RhoGTPase activity is regulated by a number of protein families: guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and guanine nucleotide-dissociation inhibitors (GDIs). This review discusses the participation of RhoGTPases and their regulators, especially GEFs in human cancers. In particular, we focus on the involvement of the RhoGTPase GEF, Vav1, a hematopoietic specific signal transducer which is involved in human neuroblastoma, pancreatic ductal carcinoma and lung cancer. Finally, we summarize recent advances in the design and application of a number of molecules that specifically target individual RhoGTPases or their regulators or effectors, and discuss their potential for cancer therapy. (C) 2010 Elsevier Inc. All rights reserved.
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