Pros and Cons of Chaperone-Mediated Autophagy in Cancer Biology

• Published in: Trends in endocrinology and metabolism Vol. 31; no. 1; pp. 53 - 66
• Main Authors: Arias, Esperanza, Cuervo, Ana Maria
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.01.2020
• Subjects: chaperones; lysosomes; metabolism; oncogenes; protein degradation; tumorigenesis; oncogenes; lysosomes; metabolism; tumorigenesis; chaperones; protein degradation
• ISSN: 1043-2760; 1879-3061
• DOI: 10.1016/j.tem.2019.09.007

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 purposes. However, growing evidence supports a physiological role for CMA in limiting malignant transformation. Understanding the mechanisms behind this functional switch of CMA from antioncogenic to pro-oncogenic is fundamental for targeting CMA in cancer treatment. We summarize current understanding of CMA functions in cancer biology and discuss the basis for its context-dependent dual role in oncogenesis. CMA is a component of the proteostasis network for protein quality control, but it has additional regulatory roles by terminating the function of key cellular proteins through their timely and selective degradation.Cells with reduced CMA have a higher facility for malignant transformation, in support of a physiological antioncogenic function of CMA.Multiple types of cancer cells and tumors upregulate CMA, and blockade of CMA reduces their tumorigenic capabilities.Cancer cells depend on CMA for a variety of pro-oncogenic functions such as sustained glycolytic activity, resistance to stressors, and maintenance of high oncogene load.The mechanisms behind the switch between the antioncogenic function of CMA in untransformed cells and its pro-oncogenic function in cancer cells remain poorly understood.