MYC disruption of the circadian metabolic cycle
One of the most important outputs of the clock is metabolic oscillation. How is metabolic oscillation affected by tumorigenesis? In the body, metabolic oscillations help us balance our food intake and energy expenditure with activity and rest. Cancer cells, in contrast, have a deregulated metabolism compared to their somatic counterparts. Tumor cells greatly increase both their nutrient uptake and biomass accumulation to fuel increased cell growth and division. MYC is one of many oncoproteins that drives altered metabolism in cancer, but we do not know how metabolic oscillations in cells or the body are altered in cancer, or if MYC disrupts these oscillations.
To study this, we will first begin to understand the origins of cell-autonomous metabolic oscillations (which were only recently appreciated in Krishnaiah et al, Cell Metabolism, 2017). We will then use genomic and metabolomics approaches to appreciate how MYC disrupts metabolic oscillations in a variety of cancer cells and models, and finally will pinpoint specific mechanisms that MYC engages to alter metabolic oscillations in cells. These studies will shed further light on how cancer cells may gain a growth advantage over their normal cell neighbors.