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Title: The regulation of cell migration and invasion by Eph-ephrin signalling
Author: Campbell, Jessica
ISNI:       0000 0004 5917 2835
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Cell migration and invasion are essential aspects of normal cellular behaviour, however abnormal cell migration can lead to defects in essential cell processes, such as wound healing, or can also promote diseases such as cancer. Cell migration can be regulated by many factors and, importantly, can depend upon a cells interaction with its surrounding cellular microenvironment. Eph receptors are the largest family of receptor tyrosine kinases and are essential in transmitting signals between cells as, uniquely to this family, the ephrin ligands are cell surface bound, therefore signalling is cell-cell contact dependent. Although Eph and ephrin functions have been studied for many years, much of the mechanisms by which they signal are still unclear. In this thesis, I have investigated the role of Eph-ephrin signalling in regulating different aspects of cell migration and invasion in prostate cancer cells and during keratinocyte cell wound healing. I find that the activity of EphB4 is regulated by the expression of PTEN phosphatase both in DU145 and PC-3 prostate cancer cells. This regulation leads to altered heterotypic cell contact inhibition of locomotion, in a co-culture assay between DU145 cells and fibroblasts. I also find that PTEN expression regulates the number of DU145 cells invading from a tumour cell spheroid, towards fibroblasts, in a 3D collagen gel. I suggest these cell behaviours may be as a consequence of altered Rac activity, downstream of EphB4 and PTEN signalling. I also use SILAC based phosphoproteomics to investigate some of the proteins regulated downstream of PTEN expression ilnd EphB4 activity. Furthermore I find that Ephrin-Bs are essential in regulating keratinocyte cell reepithelialisation during tissue culture wound healing, by regulating the actin cytoskeleton structure and E-cadherin processing. Finally, I have attempted to investigate the role of EphB2 in regulating prostate cancer cell migration and invasion, and find that EphB2 depletion does not alter PC-3 cell migration velocity in two dimensions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available