"Regulation of beta-catenin localisation and its role in tumour cell migration"

结肠癌和黑色素瘤是一个主要的健康问题，也是许多癌症相关死亡的原因。编码-连环蛋白、APC和轴蛋白的基因的种系突变增加了激活-连环蛋白并引发结肠癌进展的风险。一部分黑色素瘤与-连环蛋白基因突变有关。-连环蛋白是多功能的；它可以在外细胞膜起作用，帮助细胞以有序的方式相互粘附，或者它可以进入细胞核，在那里它参与激活触发癌症进展的基因。我们对β -连环蛋白定位的一个新方面感兴趣，当它出现在细胞膜的柔性部分时，通常与活跃的细胞迁移有关。在这项研究中，我们的目的是确定膜结合β -连环蛋白的一部分是否有助于细胞运动或肿瘤细胞侵袭。我们还将扩展我们对-连环蛋白细胞内运动的研究，以了解它的细胞核外运动是如何通过蛋白质的不同修饰或对DNA造成的损伤来调节的。这一信息将增加我们对-连环蛋白调控和功能的理解，如果成功，可能会导致发现新的途径，可以改变癌细胞中-连环蛋白的作用。

Colon cancer and melanoma are a major health problem and a cause of many cancer-associated deaths. Germ-line mutations in the genes encoding beta-catenin, APC and Axin increase the risk of activating beta-catenin and initiating the progression of colon cancer. A proportion of melanomas correlate with mutation of the beta-catenin gene. The beta-catenin protein is multi-functional; it can work at the outer cell membrane to help cells adhere to one another in an orderly manner, or it can move into the nucleus where it is involved in activating genes that trigger cancer progression. We are interested in a novel aspect of beta-catenin localisation, when it is present at flexible parts of the cell membrane which are usually associated with active cell migration. In this study we aim to determine whether a fraction of membrane-bound beta-catenin contributes to cell movement or tumour cell invasion. We also will extend our study of the intracellular movement of beta-catenin, to understand how its movement out of the nucleus is regulated by different modifications of the protein, or by damage caused to DNA. This information will increase our understanding of beta-catenin regulation and function, and if successful may lead to identifying new pathways that could be targeted to alter beta-catenin action in cancer cells.