Role of autophagy in cancer

Autophagy is a catabolic pathway used by cells to support metabolism in response to starvation and to clear damaged proteins and organelles. Autophagy can maintain tissue health and suppress degeneration and cancer initiation, and in this context autophagy is a tumor suppressor. Autophagy, however, is also a survival pathway used by both normal and cancer cells to sustain metabolism and tolerate stress, and in this context autophagy is a tumor promoter. We found that activation of a powerful oncogene such as Ras up‐regulates basal autophagy, which is required for tumor cell survival in stress and in tumorigenesis. In Ras‐expressing cells, defective autophagy causes accumulation of abnormal mitochondria, reduces oxygen consumption and causes tricarboxylic acid (TCA) cycle metabolite and energy depletion in metabolic stress. As mitochondria sustain viability of Ras‐expressing cells in starvation, autophagy is required to maintain the pool of functional mitochondria necessary to support growth and survival of Ras‐driven tumors. As cancers with Ras mutations have a poor prognosis, this “autophagy addiction” suggests that targeting autophagy and mitochondrial metabolism are valuable new approaches to treat these aggressive cancers.