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PLoS One. 2013;8(1):e53982. doi: 10.1371/journal.pone.0053982. Epub 2013 Jan 30.

P-Rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments.

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1
Beatson Institute for Cancer Research, Bearsden, Glasgow, United Kingdom.

Abstract

Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes.

PMID:
23382862
PMCID:
PMC3559689
DOI:
10.1371/journal.pone.0053982
[Indexed for MEDLINE]
Free PMC Article
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