Grant: Operating Grant

Proteases function by cutting other proteins at specific peptide bonds and are essential factors acting early in the production of bioactive molecules. Thus, they can be considered as signaling molecules themselves. The human genome encodes for 566 different proteases with 273 of these distributed extracellularly making them very attractive for therapeutic intervention. Indeed proteases currently make up a significant proportion of current drug targets. Within these extracellular proteases, two novel enzymes, matriptase and matriptase-2, have been associated with cancer, anemia and other diseases. Cancer is quickly becoming the leading cause of mortality in Canada and thus better understanding of this disease at the fundamental level, is crucial in order to provide better avenues for treatment. A cancer cell's overproduction of proteases can facilitate cancer progression and numerous studies have shown that levels of matriptase and matriptase-2 are abnormally high in many types of cancers. Furthermore, some of the proteins that are activated by these proteases are growth factors or their receptors that can sustain cancer development. Our project aims to gain further knowledge in how these two proteases get produced and how they function. We will determine how the enzymes travel from inside the cell towards the cell surface where they act. We will investigate the effect of matriptase-2 mutations associated with a form of anemia and ascertain what drives matriptase-2's capacity at suppressing tumors while matriptase supports tumor growth. We will evaluate what happens to the invasiveness of cancer cells when the expression of matriptase and/or matriptase-2 are knocked down or inhibited. We will identify proteins that interact with the proteases to assess their role in enzyme function. Using these strategies we believe our group can provide vital information as to the role of these proteases in cancer and other pathologies where deregulation leads to disease states.