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

Author

Listed:
  • Colin R. Lindsay

    (The Beatson Institute for Cancer Research)

  • Samuel Lawn

    (The Beatson Institute for Cancer Research)

  • Andrew D. Campbell

    (The Beatson Institute for Cancer Research)

  • William J. Faller

    (The Beatson Institute for Cancer Research)

  • Florian Rambow

    (Centre de Recherche, U1021 INSERM, Institut Curie, Paris 91405, France.)

  • Richard L. Mort

    (MRC Human Genetics Unit)

  • Paul Timpson

    (The Beatson Institute for Cancer Research)

  • Ang Li

    (The Beatson Institute for Cancer Research)

  • Patrizia Cammareri

    (The Beatson Institute for Cancer Research)

  • Rachel A. Ridgway

    (The Beatson Institute for Cancer Research)

  • Jennifer P. Morton

    (The Beatson Institute for Cancer Research)

  • Brendan Doyle

    (The Beatson Institute for Cancer Research)

  • Shauna Hegarty

    (School of Medicine Dentistry & Biomedical Science, Queen's University, Belfast BT7 1NN, UK.)

  • Mairin Rafferty

    (UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College, Dublin 4, Ireland.)

  • Ian G. Murphy

    (St Vincent's University Hospital, Dublin 4, Ireland.)

  • Enda W. McDermott

    (St Vincent's University Hospital, Dublin 4, Ireland.)

  • Kieran Sheahan

    (St Vincent's University Hospital, Dublin 4, Ireland.)

  • Katherine Pedone

    (Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27514, USA.)

  • Alexander J. Finn

    (Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27514, USA.)

  • Pamela A. Groben

    (Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27514, USA.)

  • Nancy E. Thomas

    (Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27514, USA.)

  • Honglin Hao

    (Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27514, USA.)

  • Craig Carson

    (Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27514, USA.)

  • Jim C. Norman

    (The Beatson Institute for Cancer Research)

  • Laura M. Machesky

    (The Beatson Institute for Cancer Research)

  • William M. Gallagher

    (UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College, Dublin 4, Ireland.)

  • Ian J. Jackson

    (MRC Human Genetics Unit)

  • Leon Van Kempen

    (McGill University/Jewish General Hospital)

  • Friedrich Beermann

    (ISREC SV EPFL)

  • Channing Der

    (Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27514, USA.)

  • Lionel Larue

    (Centre de Recherche, U1021 INSERM, Institut Curie, Paris 91405, France.)

  • Heidi C. Welch

    (The Babraham Institute)

  • Brad W. Ozanne

    (The Beatson Institute for Cancer Research)

  • Owen J. Sansom

    (The Beatson Institute for Cancer Research)

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.

Suggested Citation

  • Colin R. Lindsay & Samuel Lawn & Andrew D. Campbell & William J. Faller & Florian Rambow & Richard L. Mort & Paul Timpson & Ang Li & Patrizia Cammareri & Rachel A. Ridgway & Jennifer P. Morton & Brend, 2011. "P-Rex1 is required for efficient melanoblast migration and melanoma metastasis," Nature Communications, Nature, vol. 2(1), pages 1-9, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1560
    DOI: 10.1038/ncomms1560
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