Grant: Project Grant

The main damage done by most cancer cells results from invasion and metastasis. For this to occur, cancer cells have to leave the primary tumor and move to other tissues. Cells in our body do typically not leave their home tissue when healthy; in order for that to happen cancer cells have to change the properties of the glue that cells use to stick to their neighbors. Dr. Tepass' laboratory identifies and analyzes the components of this molecular glue that mediates adhesion between cells. The glue molecule cadherin has been shown to be broadly relevant for normal tissue development and cancer progression. Cadherin function critically depends on several other molecules including a-catenin, the focus of this study. Cadherin and a-catenin localize at the cell membrane of epithelial cells, preventing those cells from leaving the epithelium to form metastases. This is of particular significance as app. 85% of all forms of cancer derive from epithelial cells and are called carcinomas. The maintenance of epithelial tissue integrity, to which cadherin and a-catenin make major contributions, plays a pivotal role in the prevention of metastatic development in carcinomas. We use the fruit fly Drosophila as a stand-in for humans to investigate how cadherin and a-catenin govern cell behaviour. The main work in the Tepass laboratory focuses on a-catenin, which links cadherin to the cytoskeleton of the cells, an interaction that is essential for cadherin function and currently only poorly understood. Insights into how cadherin and a-catenin work normally is expected to inform us about the role of these factors in cancer, and ultimately will help develop better tools for cancer diagnosis and treatment.