期刊
PLOS ONE
卷 8, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0053982
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资金
- Cancer Research UK
- BBSRC [BBS/E/B/000C0411, BB/I02154X/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/I02154X/1, BBS/E/B/000C0411] Funding Source: researchfish
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.
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