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

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 ?. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFR?, 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? 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.

SUBMITTER: Campbell AD 

PROVIDER: S-EPMC3559689 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature