Autophagy: An Agonist and Antagonist with an Interlink of Apoptosis in Cancer

Autophagy and apoptosis are the two evolutionarily conserved processes regulating the turnover of defective organelles and other contents inside cells and damaged whole cells inside organisms, respectively. Although apoptosis and autophagy function differently, their signaling pathways are interconnected and mediated by a toggle switch that is triggered based on the requirements of a cell and its surroundings. Suppression of apoptosis and autophagy due to uncontrolled stress is thought to be a hallmark of carcinogenesis. In general, autophagy and apoptosis mediate each other through a roller coaster of up- and downregulation of factors; that is, autophagy attenuates apoptosis induction, and caspase-dependent apoptosis turns off the autophagic machinery in cancer cells, with several exceptions. Moreover, in certain scenarios, autophagy or autophagy-associated proteins induce excessive degradation of cytoplasmic components, causing “autophagic cell death.” Autophagy can also rescue cancer cells from apoptosis by modulating stress levels, determining cancer cell fate. However, the molecular signals driving the cell toward either autophagy or apoptosis remain largely unknown. Therefore, in this review, we focus on understanding the complex crossover signaling between autophagy and apoptosis pathways and their modulation in the transformation from benign proliferation to malignant carcinogenesis.