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

Ephs和相互作用的ephrin是细胞表面上的蛋白质，其使得能够在身体组织和器官内以及在肿瘤中移动的细胞定向。Eph蛋白具有酪氨酸激酶活性，在结合邻近细胞上的肝配蛋白后变得活跃。一旦激活，它们会指示这些细胞改变它们的形状和它们对基质或彼此之间的粘附，并变得更能动。在成年生物体中，Ephs和ephrin在大多数细胞中很低，但它们在许多肿瘤中重新出现。例如，当皮肤中的正常细胞（黑素细胞）变成肿瘤细胞时，它们的表面通常会有Eph和ephrin。据信，这些蛋白质现在将影响这些黑色素瘤细胞是否会迁移以及在体内的位置。在我们的研究中，我们将研究是什么控制Eph蛋白的活性。特别地，已知一类称为酪氨酸磷酸酶的酶调节酪氨酸激酶受体的功能，然而尚不清楚哪种特定的磷酸酶调节EphA3，这是我们研究的焦点。我们将发现，哪组磷酸酶调节EphA3功能，以及暴露于氧化条件（如紫外线辐射）是否也会激活Ephs并指示肿瘤细胞变得更具运动性并侵入身体的其他区域。对这种机制的了解将有助于了解黑色素瘤等癌症的病因，并可能为优化其治疗新策略提供可能性。

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.