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

  1. Anne Hakem1,
  2. Otto Sanchez-Sweatman2,
  3. Annick You-Ten1,
  4. Gordon Duncan1,
  5. Andrew Wakeham1,
  6. Rama Khokha2, and
  7. Tak W. Mak1,2,3
  1. 1Campbell Family Institute for Breast Cancer Research, Toronto, Ontario, M5G 2C1, Canada; 2Ontario Cancer Institute, Toronto, Ontario, M5G 2C1, Canada

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.

Keywords

Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1310805.

  • 3 Corresponding author.

    3 E-MAIL tmak{at}uhnres.utoronto.ca; FAX (416) 204-5300.

    • Accepted June 24, 2005.
    • Received February 25, 2005.
| Table of Contents

Life Science Alliance