The tumor suppressor protein, p53 responds to cellular stress such as DNA damage, oncogenic activation and hypoxia by transactivating downstream genes that are responsible for apoptosis, DNA repair, senescence, cell cycle arrest and cell cycle progression. However, emerging trends show that p53 also plays multifaceted roles in regulating glucose metabolism. It promotes oxidative phosphorylation, suppresses glycolysis at multiple points as well as controlling glutamine and lipid metabolism. Current findings suggest that p53 actions have potential to influence the Warburg Effect, that is, characteristic of cancer cells. The Warburg phenomenon is characterized by their preference for glycolysis to oxidative phosphorylation for ATP generation, irrespective of adequate oxygen supply. This is often in concomitance with enhanced glucose uptake and leads to increased lactate production and anabolic processes such as lipid synthesis and de novo nucleic acid synthesis. The molecular underpinnings of the Warburg Effect are still poorly understood. These important differences between cancer and normal cells have induced interest in glucose metabolism as a drug target. This chapter focuses on the influence p53 exerts on glucose metabolism as well as on the implications of the Warburg phenomenon in carcinogenesis and a review of the ever-increasing number of p53 regulators.
Part of the book: Neoplasm