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

Lindsay, Colin R. and Lawn, Samuel and Campbell, Andrew D. and Faller, William J. and Rambow, Florian and Mort, Richard L. and Timpson, Paul and Li, Ang and Cammareri, Patrizia and Ridgway, Rachel A. and Morton, Jennifer P. and Doyle, Brendan and Hegarty, Shauna and Rafferty, Mairin and Murphy, Ian G. and McDermott, Enda W. and Sheahan, Kieran and Pedone, Katherine and Finn, Alexander J. and Groben, Pamela A. and Thomas, Nancy E. and Hao, Honglin and Carson, Craig and Norman, Jim C. and Machesky, Laura M. and Gallagher, William M. and Jackson, Ian J. and Van Kempen, Leon and Beermann, Friedrich and Der, Channing and Larue, Lionel and Welch, Heidi C. and Ozanne, Brad W. and Sansom, Owen J. (2011) P-Rex1 is required for efficient melanoblast migration and melanoma metastasis. Nature Communications, 2. ISSN 2041-1723

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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:
Journal Article
Journal or Publication Title:
Nature Communications
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/3100
Subjects:
ID Code:
84132
Deposited By:
Deposited On:
20 Jan 2017 14:08
Refereed?:
Yes
Published?:
Published
Last Modified:
23 Sep 2020 03:19