Molecular dissection of the role of ARAP3 in angiogenesis

在胚胎发育过程中，专门的组织形成。例如，需要循环系统来滋养发育中的有机体。这个过程被称为血管生成。血管生成在癌症中也很重要，新的肿瘤需要血液供应才能得到营养。当我们研究一只缺乏ARAP3的小鼠并看到胚胎死亡是因为它们不能形成血管时，我们发现一种新的信号蛋白ARAP3是血管生成所必需的。我们想要确定为什么ARAP3是血管生成所必需的，以及它是否可以成为癌症治疗的良好靶点。为此，我们将研究ARAP3是如何被控制的，并在长期内控制其他细胞蛋白质。我们将分析小鼠胚胎中的血管，这些胚胎要么缺乏ARAP3，要么含有微小的变化(突变)。其次，我们将研究缺乏ARAP3或含有突变的ARAP3蛋白的内皮细胞(形成血管)，看看它们与正常细胞有何不同。最后，我们将把ARAP3或其突变体重新植入血管内皮细胞，以“拯救”它们。通过这种方式，我们将了解为什么ARAP3是血管生成所必需的，以及它是否是一个很好的抗癌药物靶点。

During embryonic development, specialised tissues form. For example, a circulatory system is required to nourish the developing organism. This process is called angiogenesis. Angiogenesis is also important in cancer, where new tumours need to be provided with blood so they can be nourished. We found out that ARAP3, a new signalling protein, is needed for angiogenesis when we studied a mouse that lacked ARAP3 and saw that the embryos died because they couldn’t form blood vessels. We want to establish why ARAP3 is required for angiogenesis, and whether it could be a good target for cancer treatment. For this, we will look at the way in which ARAP3 is controlled and in term controls other cellular proteins. We will analyse vessels in mouse embryos, which either lack ARAP3 or where it contains a small change (mutation). Secondly, we will study endothelial cells (which form blood vessels) lacking ARAP3, or containing the mutant ARAP3 protein, to see how they differ from normal cells. Finally, we will put ARAP3, or its mutants back into endothelial cells, to ‘rescue’ them. In this way we will learn why ARAP3 is required for angiogenesis, and whether it is a good cancer drug target.