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

Cell Signal. 2011 Jun;23(6):969-79. doi: 10.1016/j.cellsig.2010.10.022. Epub 2010 Oct 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Movement
  • Cytoskeleton / metabolism
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Guanine Nucleotide Dissociation Inhibitors / genetics
  • Guanine Nucleotide Dissociation Inhibitors / metabolism
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Immunity, Cellular
  • Mutation
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Proto-Oncogene Proteins c-vav / genetics
  • Proto-Oncogene Proteins c-vav / immunology
  • Proto-Oncogene Proteins c-vav / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • rho GTP-Binding Proteins / metabolism*


  • GTPase-Activating Proteins
  • Guanine Nucleotide Dissociation Inhibitors
  • Guanine Nucleotide Exchange Factors
  • Proto-Oncogene Proteins c-vav
  • Transcription Factors
  • rho GTP-Binding Proteins