Funded by the Constellation Gold Network Distributors
Cancer is a disease of uncontrolled cell growth. As the disease advances, the cancer can leave the original site and spread to other parts of the body. The ability to grow and invade is energetically costly though. Thus, cancer cells will modify their metabolism to meet these high energy requirements. This includes aggressively using nutrients to produce more energy (ATP), making building blocks for growth (protein, plasma membranes, DNA) and finding ways to overcome metabolic stress (e.g., reactive oxygen species). In other words, if we can identify metabolic changes that occur only in cancer, then impacting the altered metabolic pathways could enable us to selectively kill cancer cells and not impact normal cells.
We are interested in the metabolism of the sugar molecules fructose and mannose. Cells generate mannose-related metabolites from fructose. We discovered that the balance between fructose and mannose is important when lung cancer becomes aggressive. Only these aggressive lung cancer cells were killed when the conversion of fructose to mannose was disrupted. This project will examine how fructose-mannose metabolism is changed when lung cancer becomes aggressive. We will also determine why this metabolic pathway is critical to keep these cancer cells alive. To accomplish the task, we will remove a critical enzyme in fructose -mannose metabolism, and then utilize a series of experiments to characterize the metabolism of these cancer cells. If successful, this study will provide clues as to why drinking soda (fructose) can increase cancer risk while consuming mannose slows tumor growth. Ultimately, we want to answer whether targeting this sugar pathway can help treat patients.