The multiple roles of autophagy in uveal melanoma and the microenvironment

Abstract

Purpose: Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults, and effective clinical treatment strategies are still lacking. Autophagy is a lysosome-dependent degradation system that can encapsulate abnormal proteins, damaged organelles. However, dysfunctional autophagy has multiple types and plays a complex role in tumorigenicity depending on many factors, such as tumor stage, microenvironment, signaling pathway activation, and application of autophagic drugs.

Methods: A systematic review of the literature was conducted to analyze the role of autophagy in UM, as well as describing the development of autophagic drugs and the link between autophagy and the tumor microenvironment.

Results: In this review, we summarize current research advances regarding the types of autophagy, the mechanisms of autophagy, the application of autophagy inhibitors or agonists, autophagy and the tumor microenvironment. Finally, we also discuss the relationship between autophagy and UM.

Conclusion: Understanding the molecular mechanisms of how autophagy differentially affects tumor progression may help to design better therapeutic regimens to prevent and treat UM.

Keywords: Autophagy; Drug target; Microenvironment; Uveal melanoma.

Fig. 1

The schematic illustration of the autophagy types. A The process of macroautophagy formation; B the process of microautophagy formation; C the process of chaperone-mediated autophagy formation

Fig. 2

The schematic illustration of the autophagy mechanism. A Initiation: activation of multiple ATG proteins are engaged and localized to Pre-autophagosomal structure; B Nucleation: ATG proteins and lipids are recruited to form phagophore; C Maturation: completion and transport of the autophagosome by ATG proteins; D Fusion: docking and fusion between autophagosome and lysosome; E Degradation: degradation of the cargos inside the autolysosome.

Fig. 3

The schematic illustration of the autophagy and the tumor microenvironment. A Autophagy interacts with Cancer-associated fibroblast; B autophagy interacts with Mesenchymal stem cell; C autophagy plays a role in angiogenesis by affecting endothelial cells. D Autophagy can affect the regulatory T cells, NK-and CTL-mediated cell cleavage and immune checkpoints