Pros and Cons of Chaperone-Mediated Autophagy in Cancer Biology

Autophagy contributes to cellular quality control and energetics through lysosomal breakdown and recycling of essential cellular components. Chaperone-mediated autophagy (CMA) adds to these autophagic functions the ability to timely and selectively degrade single tagged proteins to terminate their cellular function and, in this way, participate in the regulation of multiplE cellular processes. Many cancer cells upregulate CMA for protumorigenic and prosurvival pur poses. However, growing evidence supports a physiological role for CMA in limiting malignant transformation. Understanding the mechanisms behind this functional switch of CMA from anti oncogenic to pro-oncogenic is fundamental for targeting CMA in cancer treatment. We summa rize current understanding of CMA functions in cancer biology and discuss the basis for it context-dependent dual role in oncogenesis.