Abstract

The MYC oncogene, which encodes a master transcriptional regulator of proliferative metabolism, is commonly deregulated in human cancers. Genomics studies of MYC reveal its genome-wide effect on transcription by relieving RNA polymerase pausing. MYC ’s expression in normal cells is tightly regulated such that growth factor withdrawal or nutrient deprivation silence MYC expression, keeping normal cells in a non-proliferative state. By contrast, cancer cells with deregulated MYC undergo a forced program of growth, due to MYC ’s induction of ribosome biogenesis and macromolecular synthesis, which renders these cells addicted to nutrients to support a ‘run-away’ program of cell growth and proliferation. As such, withdrawal of nutrients or interruption of specific metabolic pathways with inhibitors could curb MYC -induced cancer development. Most recently, MYC was found to disrupt the circadian clock transcriptional network and circadian metabolism, presumably to allow unrestrained metabolism that supports growth of a MYC -driven cancer cell. It is also uncovered in unpublished work that MYC induces a previously unsuspected rapidly oscillation of intracellular metabolites that could result from hyper-coupling of metabolic oscillators.