Grant: Operating Grant

Cancer is the first cause of death in Canada. Colorectal cancers are among the most common and lethal malignancies. This cancer has a poor prognosis in advanced stages due to its resistance to conventional therapies. Cancer cells have developed means to resist to treatments and one of them is called autophagy. Autophagy is the process by which cells degrade and recycle their own constituents. Importantly, autophagy is induced by the lack of nutrients, and cancer cells often grow in environments lacking proper blood supply. Hence, a large proportion of cancer cells rely on autophagy to stay alive. Cells of the body are composed of multiple types of membranes. These membranes are highly controlled and the mechanisms regulating them are collectively called 'membrane trafficking'. Autophagy is vastly controlled by membrane trafficking events. Thus, understanding how membrane trafficking regulates autophagy is important to find new cancer therapeutic avenues. My work has identified regulators of membrane traffic necessary for autophagy. I found their function to be temporally controlled. Their activation and the recruitment of specific effectors (molecular helpers) is important for autophagy progression. Moreover, I identified regulators of membrane trafficking and autophagy required for the growth of colorectal cancer cells. In this proposal, we will characterize how one regulator of membrane trafficking is activated and inhibited by specific proteins, and how it recruits specific effectors to control autophagy. Importantly, we will test the newly identified components and aspects of their temporal regulation for their roles in autophagy in normal cells and for their requirements in colorectal cancer cell growth. This work will represent a key step in understanding how we can specifically target and eliminate colorectal cancer cells through the modulation of membrane trafficking.