Role of autophagy in tumorigenesis

Abstract

Autophagy is an evolutionarily conserved cytoplasmic degradation pathway. A fundamental function of autophagy at the cellular level is to recycle cytoplasmic components, including macromolecules and organelles. Autophagy is essential for cell survival under nutrient deprived conditions. In addition, working in concert with other proteins in cells, the regulated and cargo-specific autophagic degradation is crucial for cellular maintenance and reducing cellular damage. Since the initial reports that autophagy is implicated in tumor suppression more than a decade ago, great advancements have been made in research on both autophagy and on its role in tumorigenesis. Here we summarize some of the important results from literature, mostly mouse genetics and human cancer genetics data. These data support a working model that autophagy suppresses tumorigenesis primarily in a cellintrinsic and indirect manner, most likely through reducing cellular damage by degrading some tissue-specific cell-damaging factors. In addition, non-cell autonomous processes triggered by autophagy defect may also contribute to tumor development. The current information on the unequivocal role of autophagy in suppressing tumorigenesis strongly favors future exploration in area of developing practical autophagy activating approaches for tumor chemoprevention.