RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis

Genes Dev. 2005 Sep 1;19(17):1974-9. doi: 10.1101/gad.1310805. Epub 2005 Aug 17.

Abstract

The Rho proteins are Ras-related guanosine triphosphatases (GTPases) that function in cytoskeletal reorganization, cell migration, and stress fiber and focal adhesion formation. Overexpression of RhoC enhances the ability of melanoma cells to exit the blood and colonize the lungs. However, in vivo confirmation of RhoC's role in metastasis has awaited a RhoC-deficient mouse model. Here we report the generation of RhoC-deficient mice and show that RhoC is dispensable for embryonic and post-natal development. We demonstrate that loss of RhoC does not affect tumor development but decreases tumor cell motility and metastatic cell survival leading to a drastic inhibition of metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Cell Movement
  • Cell Survival
  • Cell Transformation, Neoplastic
  • Embryonic Development / physiology*
  • Female
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasm Metastasis / pathology
  • Neoplasm Metastasis / physiopathology*
  • Neoplasms, Experimental / etiology*
  • Neoplasms, Experimental / pathology
  • Pregnancy
  • T-Lymphocytes / immunology
  • ras Proteins
  • rho GTP-Binding Proteins / deficiency
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / immunology
  • rho GTP-Binding Proteins / physiology*
  • rhoC GTP-Binding Protein

Substances

  • Rhoc protein, mouse
  • ras Proteins
  • rho GTP-Binding Proteins
  • rhoC GTP-Binding Protein