Functions and Implications of Autophagy in Colon Cancer

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.

Keywords: autophagy; cancer; colon; nutrient.

Figure 1

Overview of autophagy subtypes; macro-autophagy, micro-autophagy, and CMA. Specifically, highlighting examples of selective macro-autophagy.

Figure 2

Schematic of the tumor microenvironment highlighting the impact of autophagy. Cell autonomous roles of autophagy in immune, epithelial or, the cross-talk between cell types in colorectal cancer.

Figure 3

Schematic summarizing (A) Simplified overview of mechanisms of mTORC1 regulation. and (B) how nutrient modulation impacts autophagy. Bolded mechanisms indicate data from non-CRC samples. Please refer to text for detailed mechanisms.