Guanine nucleotide exchange factors for RhoGTPases: good therapeutic targets for cancer therapy?

Abstract:

: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.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Lazer G,Katzav S

doi

10.1016/j.cellsig.2010.10.022

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

969-79

issue

6

eissn

0898-6568

issn

1873-3913

pii

S0898-6568(10)00309-8

journal_volume

23

pub_type

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