Defining the functions of the actin bundling protein fascin in invasive, collective cell migration

Cell migration, or the movement of a cell, is an essential process in the body. However, most research has focused on how individual cells migrate rather than how groups, or collectives, of cells migrate. Understanding collective cell migration is critical because many cells in our bodies migrate as collectives. During embryonic development, many cells collectively migrate to form the tissues and organs. However, in diseases such as cancer, collective cell migration can be hijacked to lead to cancer metastasis, the process by which cancer spreads throughout the body. One of the proteins known to play a role in cell migration is Fascin. Fascin promotes migration and metastasis in many types of cancer, leading to more aggressive disease. Yet how Fascin promotes collective cell migration is not well understood. Here, I use a model of collective cell migration in the ovary of the fruit fly, Drosophila melanogaster, called border cell migration. I found that Fascin acts both in the migrating cells and their surroundings to promote border cell migration. I also discovered that Fascin promotes border cell migration in many different ways, including regulating the stiffness of the migrating cells and their surroundings. These new functions of Fascin may lead to a better understanding of how Fascin promotes collective cell migrations in humans, such as in cancer metastasis. Ultimately, the work presented in this thesis demonstrates how the border cell migration, in the fruit fly, can be used as a model to better understand the mechanisms driving human diseases such as cancer metastasis.