Grant: Operating Grant

Cell motility or migration is an important process that determines many physiological events, including development, tissue repair, and immune responses. Migration is controlled by the interactions between the cell and the surrounding matrix that are co-ordinated with the continual re-organization of the structural elements within a cell (the cytoskeleton) that determine its shape. Proteins at the cell surface called integrins are the nodes of this co-ordination, as they form contacts with the matrix and relay these signals to the cytoskeleton. Integrin-mediated signal relay is highly complex and involves a multi-protein communication network within the cell. Furthering our understanding of this network and how its components function will allow us to pinpoint molecular alterations in diseases involving aberrant cell migration, notably cancer. Cancer mortality usually arises as a result of tumor cell migration to new sites in the body, with the consequent formation of new tumors. We have discovered that a molecule called PTPa plays key roles in the integrin signaling network, as it performs two different functions in this process. Our previous work has shown that PTPa acts in conjunction with integrins to stimulate early signaling molecules. We have recently identified another requirement for PTPa further along in the signaling relay that is critical for migration. In our proposed research we will elucidate this novel second role of PTPa that we believe is fundamental to the migration of numerous cell types. Knowledge of precise molecular functions in integrin signaling will promote the development of targeted molecular therapies, perhaps to PTPa, to combat migration-based diseases.