Molecular regulation of autophagy and its role in cancer

Autophagy or ‘self eating’ is a complex cellular process involving lysosomal-mediated degradation and recycling of intracellular macromolecules, including protein aggregates and damaged organelles. There are three types of autophagic pathways, namely, macroautophagy (or ‘'autophagy'’), microautophagy and chaperone-mediated autophagy, varying in their routes to lysosomes. Autophagy plays stage-dependent dual roles in cancer, i.e., tumor suppression and tumor progression. During tumor initiation, removal of defective organelles, prevention of DNA damage and reduction of oxidative stress accounts for the tumor- suppressive function of autophagy. Conversely, during the later stages of tumor development, autophagy promotes tumor cell proliferation via providing nutrient and energy from degraded macromolecules to withstand the metabolic stress. The molecular control of autophagy in cancer is governed by mTOR, DAP kinase, p53 and ERK signaling pathways as well as its pro and anti-metastatic function. Autophagy plays a complex role in these cancer-related signaling pathways; thereby targeting the autophagy-related pathways can be a promising tool for developing inventive strategies in cancer therapeutics. In this review, we focus on the molecular mechanism of autophagy coinciding with pathways governing tumor production.