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

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

Author information

1
The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.

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.

PMID:
22109529
PMCID:
PMC3400057
DOI:
10.1038/ncomms1560
[Indexed for MEDLINE]
Free PMC Article

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