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

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, Brendan Doyle, Shauna Hegarty, Mairin Rafferty, Ian G. Murphy, Enda W. McDermott, Kieran Sheahan, Katherine Pedone, Alexander J. Finn, Pamela A. Groben, Nancy E. Thomas, Honglin Hao, Craig Carson, Jim C. Norman, Laura M. Machesky, William M. Gallagher, Ian J. Jackson, Leon Van Kempen, Friedrich Beermann, Channing Der, Lionel Larue, Heidi C. Welch, Brad W. Ozanne and Owen J. Sansom ()
Additional contact information
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

Nature Communications, 2011, vol. 2, issue 1, 1-9

Abstract: 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.

Date: 2011
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DOI: 10.1038/ncomms1560

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