title: P-Rex1 cooperates with PDGFRβ 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 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.
authors: Beatson Institute for Cancer Research, Bearsden, Glasgow, United Kingdom.
authors: Andrew D
authors: AD
authors: Campbell
authors: Samuel
authors: S
authors: Lawn
authors: Lynn C
authors: LC
authors: McGarry
authors: Heidi C
authors: HC
authors: Welch
authors: Bradford W
authors: BW
authors: Ozanne
authors: Jim C
authors: JC
authors: Norman
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D046911:Macromolecular Substances; C453280:PREX1 protein, human; D034741:RNA, Small Interfering; D020797:Receptor, Platelet-Derived Growth Factor beta
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