The role of protein tyrosine phosphatases regulating Eph RTK-signalling and modulating invasive tumour cell properties.

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The Ephs and interacting ephrins are proteins on the cell surface, which enable orientation of cells that move within the body tissues and organs, but also in tumours. Eph proteins have tyrosine kinase enzyme activity that becomes active after binding ephrins on neighbouring cells. Once active, they instruct these cells to change their shape and their adhesion to the substratum or between each other, and to become more motile. In adult organisms Ephs and ephrins are low in most cells, but they re-appear in many tumors. For example, when normal cells in the skin (melanocytes) become tumor cells, they often will have Ephs and ephrins on their surface. It is believed that these proteins will now affect if these melanoma cells will migrate and to which locations within the body. In our studies we will examine what controls the activity of Eph proteins. In particular, a class of enzymes called tyrosine phosphatases are known to regulate the function of tyrosine kinase receptors, however it is not clear which particular phosphatase regulates EphA3, the focus of our studies. We will find out, which set of phosphatases regulates EphA3 function and whether exposure to oxidative conditions, such as UV radiation, also activates Ephs and instructs tumour cells to become more motile and to invade other areas of the body. The understanding of this mechanism will help to understand the cause of cancers such as melanoma and might offer possibilities to optimise new strategies for its treatment.