Grant: Team Grant: Terry Fox New Frontiers Program in Cancer

Cancer cells are different from normal cells in various aspects,one of which is the way they use energy. The main objective of this team program is to establish the link between the usage of energy and cancerous cells behavior. The team brings together scientists performing fundamental as well as clinical research, who will together study how an abnormal usage of energy by cells can lead to cancer initiation and further tumor progression. We present here a program integrating five programs, all linked to the interest of understanding cancer bioenergetics, and using common resources and techniques to achieve this goal.The first project involves the study of the way cancer cells can sense the nutrients available in their environment. To support cancer growth, cells present in a tumor modify the way they use glucose as a source of energy, a modification termed the Warburg effect.The role of a molecule called AMPkinase will be specifically studied as it has been shown to potentially be an important sensor contributing to this effect. The second project will further our understanding by studying the role of a protein complex including a nutrient sensor AMPkinase and another molecule called BHD/Folliculin, which work together in the adaptation of the cancer cells to the stress brought on by the environment of the growing tumor. The third project aims to find the best therapeutic drug strategy to activate AMPkinase in order to mimic a decrease in caloric supply, and potentially inhibit tumor growth. The fourth project will integrate this information and look at the bigger picture and study the roles of different signaling molecules involved in pathways, which can lead to the increase, or decrease of this energy sensing in the cells. Finally, the fifth project will address the question of how the regulation of our genes involved in the body energy balance could modulate cancer cell behavior. Our team will study metabolism towards understanding,preventing & treating cancer.