P-Rex1 is required for efficient melanoblast migration and melanoma metastasis

Nat Commun. 2011 Nov 22;2:555. doi: 10.1038/ncomms1560.

Abstract

Metastases are the major cause of death from melanoma, a skin cancer that has the fastest rising incidence of any malignancy in the Western world. Molecular pathways that drive melanoblast migration in development are believed to underpin the movement and ultimately the metastasis of melanoma. Here we show that mice lacking P-Rex1, a Rac-specific Rho GTPase guanine nucleotide exchange factor, have a melanoblast migration defect during development evidenced by a white belly. Moreover, these P-Rex1(-/-) mice are resistant to metastasis when crossed to a murine model of melanoma. Mechanistically, this is associated with P-Rex1 driving invasion in a Rac-dependent manner. P-Rex1 is elevated in the majority of human melanoma cell lines and tumour tissue. We conclude that P-Rex1 has an important role in melanoblast migration and cancer progression to metastasis in mice and humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Cells, Cultured
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / physiopathology*
  • Tissue Array Analysis

Substances

  • Guanine Nucleotide Exchange Factors
  • PREX1 protein, mouse