P-Rex1 Cooperates with PDGFR[beta] to Drive Cellular Migration in 3D Microenvironments

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 f...

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Bibliographic Details
Published in:PloS one 2013-01, Vol.8 (1), p.e53982
Main Authors: Campbell, Andrew D, Lawn, Samuel, McGarry, Lynn C, Welch, Heidi C, Ozanne, Bradford W, Norman, Jim C
Format: Article
Language:English
Subjects:
Cancer metastasis
Physiological aspects
Platelet-derived growth factor
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Summary: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 [beta]. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFR[beta], 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 PDGFR[beta] 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0053982