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

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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.