Abstract
Autophagy is an essential function to breakdown cellular proteins and organelles to recycle for new nutrient building blocks. In colorectal cancer, the importance of autophagy is becoming widely recognized as it demonstrates both pro- and anti-tumorigenic functions. In colon cancer, cell autonomous and non-autonomous roles for autophagy are essential in growth and progression. However, the mechanisms downstream of autophagy (to reduce or enhance tumor growth) are not well known. Additionally, the signals that activate and coordinate autophagy for tumor cell growth and survival are not clear. Here, we highlight the context- and cargo-dependent role of autophagy in proliferation, cell death, and cargo breakdown.
Highlights
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States
Hyper-activation of molecular target of rapamycin complex 1 (mTORC1), a known pathway of nutrient sensing, contributes to cell proliferation and tumor progression. mTORC1 is activated in about 50% of CRC
Non-selective autophagy is used for nutrient stress while selective autophagy is used for cell maintenance
Summary
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Survival rates have improved in the last three decades due to early detection, patients diagnosed at later stages of disease have a 5-year survival rate of 14% [2,3] Treatments available for these patients are limited, it is important to better understand tumor development and identify targeted therapies to improve overall patient care. Under several different cell stressors, autophagy is activated through kinase signaling and transcriptional activation by serine/threonine protein kinase 1 (ULK1) and transcription factor EB (TFEB). This activates a cascade of autophagy-related genes (ATG) [9], and formation of a spherical double layer membrane termed the autophagosome. We highlight cellular pathways that regulate autophagy, selective forms of autophagy, and how these mechanisms target different cargo for degradation
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