Role of the metabolic stress responses of apoptosis and autophagy in tumor suppression.

Metabolic stress is an important stimulus that promotes apoptosis-mediated tumor suppression. Metabolic stress arises in tumors from multiple factors that include insufficient nutrient supply caused by deficient angiogenesis and high metabolic demand of unrestrained cell proliferation. The high metabolic demand of tumor cells is only exacerbated by reliance on the inefficient process of glycolysis for energy production. Recently it has become clear that tumor cells survive metabolic stress through the catabolic process of autophagy. Autophagy also functions as a tumor suppression mechanism by preventing cell death and inflammation and by protecting the genome from damage and genetic instability. How autophagy protects the genome is not yet clear but may be related to its roles in sustaining metabolism or in the clearance of damaged proteins and organelles and the mitigation of oxidative stress. These findings illuminate the important role of metabolism in cancer progression and provide specific predictions for metabolic modulation in cancer therapy.