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 was shown to be broadly relevant for normal tissue development and cancer progression. Cadherin function critically depends on several other molecules including alpha-Catenin and other proteins that together form the adherens junction. These cellular junctions are engaged in maintaining normal tissue shape of epithelia, and in preventing cells from leaving the epithelium to form metastases. This is of particular significance as most forms of cancer called carcinomas derive from epithelial cells. We use the fruit fly Drosophila as a stand-in for humans to investigate how adherens junction proteins govern cell behaviour. The main work in the Tepass laboratory will focus on alpha-Catenin and other proteins that link transmembrane cadherin to the cytoskeleton, an interaction that is essential for cadherin function and currently only poorly understood. Insights into how adherens junctions normally operate is expected to inform us about the role of these factors in cancer and other pathologies, and ultimately will help develop better tools for disease diagnosis and treatment.