Xenophagy in cancer

Abstract

Macroautophagy (herein autophagy) is an intracellular pathway in which cytoplasmic components are captured by double-membrane vesicles (autophagosomes) that eventually fuse with lysosomes to degrade the cargo. Basal levels of autophagy in all eukaryotic cells maintain cellular homeostasis and under conditions of stress, organelles and proteins not essential for survival are degraded. Apart from these functions, cargoes like aggregated proteins, damaged organelles and intracellular pathogens, which are otherwise harmful to cells, are also selectively captured by autophagy and are destined for degradation. In terms of infectious diseases, pathogens are cleared by a specific form of autophagy known as xenophagy. This lysosomal mediated degradation of pathogens also increases the antigen presentation of cells thereby inducing a further immune response. The process of xenophagy provides a broad spectrum of defense mechanism to capture bacterial, viral and protozoan pathogens. However, pathogens have developed ingenious mechanisms to modulate xenophagy to enhance their intracellular survival. Meanwhile, certain pathogens also induce deleterious effects such as chronic inflammation and overexpression of oncogenes in the host system. This over time can increase the susceptibility of the host for tumorigenesis. Hence targeting tumor through anti-microbial mechanisms like xenophagy could be a novel strategy for combinatorial anti-cancer therapy. The recent developments in understanding the role of xenophagy in combating cancer causing pathogens will be discussed in this review.

Keywords: Cancer; Carcinogenesis; Infection; Inflammation; Xenophagy.