Background and Aims: Cells need to migrate away from their microenvironment to enable the tumour to metastasise. The growth factors Epidermal Growth Factor (EGF) and Transforming Growth Factor α (TGFα) stimulate the migration of fibroblasts into 3D collagen gels. Experiments using a number of growth factors concluded that some stimulated Akt phosphorylation whilst others reduced the phosphorylation of this pathway, but all stimulated migration; suggesting that multiple pathways are important for cell motility. EGF-R upon activation by ligand is phosphorylated at a number of residues. Each phosphorylated residue in turn stimulates specific signalling pathways. The aim of the project is to determine which of these pathways is important for cell motility.
Methodology: Boyden chamber assay will be utilised to investigate the effects of specific kinase inhibitors on the migration of cells in the presence of EGF. Direct methods such as phospho-specific Western blotting will study the effect of EGF on phosphorylation of EGF-R.