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

Lindsay, C.C.R. et al. (2011) P-Rex1 is required for efficient melanoblast migration and melanoma metastasis. Nature Communications, 2, pp. 1-9. (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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Li, Mr Ang and Machesky, Professor Laura and Lindsay, Dr Colin and Timpson, Dr Paul and Lawn, Mr Samuel and Norman, Dr James and Faller, Dr William and Ozanne, Professor Bradford and Morton, Professor Jen and Doyle, Dr Brendan and Ridgway, Dr Rachel and Sansom, Professor Owen and Campbell, Dr Andrew
• Authors: Lindsay, C.C.R., Lawn, S., Campbell, A.D., Faller, W.J., Rambow, F., Li, A., Cammareri, P., Ridgway, R.A., Morton, J.P., Doyle, B., Hegarty, S., Rafferty, M., Murphy, I.G., McDermott, E.W., Sheahan, K., Pedone, K., Finn, A.J., Groben, P.A., Thomas, N.e., Hao, H., Carson, C., Norman, J.C., Machesky, L.M., Gallagher, W.M., Jackson, I.J., Van Kempen, L., Beermann, F., Der, C., Larue, L., Welch, H.C., Ozanne, B.W., Sansom, O.J., and Timpson, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Communications
• Publisher: Nature Publishing Group
• ISSN: 2041-1723
• ISSN (Online): ESSN: 2041-1723
• Published Online: 01 November 2011