The role for autophagy in cancer

Abstract

Autophagy is a survival-promoting pathway that captures, degrades, and recycles intracellular proteins and organelles in lysosomes. Autophagy preserves organelle function, prevents the toxic buildup of cellular waste products, and provides substrates to sustain metabolism in starvation. Although in some contexts autophagy suppresses tumorigenesis, in most contexts autophagy facilitates tumorigenesis. Cancers can upregulate autophagy to survive microenvironmental stress and to increase growth and aggressiveness. Mechanisms by which autophagy promotes cancer include suppressing induction of the p53 tumor suppressor protein and maintaining metabolic function of mitochondria. Efforts to inhibit autophagy to improve cancer therapy have thereby attracted great interest.

Figure 1. Proposed tumor-suppressing and tumor-promoting roles for autophagy in cancer.

(A) Proposed mechanisms by which autophagy may suppress tumorigenesis. Autophagy defects impair tissue health, leading to chronic tissue damage and regeneration that may create an environment that promotes cancer. (B) Proposed mechanisms by which autophagy promotes cancer by limiting stress responses and supporting metabolism and survival.