Grant: Project Grant

Most cells that give rise to cancer in the skin, breast, lung, colon or other organs have a common feature: they are epithelial cells. Epithelial cells must lose their characteristic cell shape either partially or completely to initiate tumour formation and/or invade other organs to form metastases. This process is called epithelial-mesenchymal transition (EMT) and is a key step in cancer progression. We will study EMT in a novel and unique model to gain insight into cancer that will ultimately help to diagnose and combat cancer. Epithelial cells are held together by a molecular glue called adherens junctions. These structures prevent epithelial cells from migration to other organs causing metastases. It has been established that the loss of adherens junctions occurs during EMTs and is a key early step in promoting cancer. Moreover, epithelial cells have a pronounced apical-basal polarity which is the central organizing principle of these cells, and the loss of polarity is an important early step in EMT. We have established a model in which the loss of polarity and adherens junctions during EMTs can be investigated with unprecedented clarity and is analyzed with computational tools that reveal details of the process that have not been seen before. The application of state-of-the-art live imaging approaches has greatly advanced our understanding of how cell change shape and molecules control cell behavior in recent years. EMTs occur in cancer but also in normal development, and the underlying mechanisms are believed to be essentially the same. Cells in the fruit fly embryo that give rise to the nervous system (neural stem cells) undergo an EMT-like process in a context that is uniquely accessible to advanced live imaging methods. Fruit flies are a proven model in cancer research, combining the powerful genetic and molecular tools available in the fly with our state-of-the-art imaging capabilities, and the ongoing development of computational tools.