P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

Campbell, A.D., Lawn, S., McGarry, L.C., Welch, H.C., Ozanne, B.W. and Norman, J.C. (2013) P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments. PLoS ONE, 8(1), e53982. (doi: 10.1371/journal.pone.0053982) (PMID:23382862) (PMCID:PMC3559689)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McGarry, Ms Lynn and Ozanne, Professor Bradford and Norman, Professor James and Lawn, Mr Samuel and Campbell, Dr Andrew
• Authors: Campbell, A.D., Lawn, S., McGarry, L.C., Welch, H.C., Ozanne, B.W., and Norman, J.C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Published Online: 30 January 2013
• Copyright Holders: Copyright © 2013 The Authors
• First Published: First published in PLoS ONE 8(1):e53982
• Publisher Policy: Reproduced under a Creative Commons License