Dual role of autophagy in hallmarks of cancer

Abstract

Evolutionarily conserved across eukaryotic cells, macroautophagy (herein autophagy) is an intracellular catabolic degradative process targeting damaged and superfluous cellular proteins, organelles, and other cytoplasmic components. Mechanistically, it involves formation of double-membrane vesicles called autophagosomes that capture cytosolic cargo and deliver it to lysosomes, wherein the breakdown products are eventually recycled back to the cytoplasm. Dysregulation of autophagy often results in various disease manifestations, including neurodegeneration, microbial infections, and cancer. In the case of cancer, extensive attention has been devoted to understanding the paradoxical roles of autophagy in tumor suppression and tumor promotion. In this review, while we summarize how this self-eating process is implicated at various stages of tumorigenesis, most importantly, we address the link between autophagy and hallmarks of cancer. This would eventually provide a better understanding of tumor dependence on autophagy. We also discuss how therapeutics targeting autophagy can counter various transformations involved in tumorigenesis. Finally, this review will provide a novel insight into the mutational landscapes of autophagy-related genes in several human cancers, using genetic information collected from an array of cancers.

FUN14 Domain‐Containing 1–Mediated Mitophagy Suppresses Hepatocarcinogenesis by Inhibition of Inflammasome Activation in Mice

“…These data suggest that up‐regulation of FUNDC1 expression is required for and benefits the late stage of tumor development. It is thus proposed that mitophagy, a selective form of macroautophagy, has dual roles in cancer . Our findings are consistent with the established dual role of general autophagy in cancer.…”

Targeting autophagy using metallic nanoparticles: a promising strategy for cancer treatment

“…Some studies support the idea that, in established tumors, constitutive autophagy may have a protective role in cancer cells by removing damaged organelles or recycling misfolded macromolecules [47]. In support of this hypothesis, several studies report that autophagy tries to fulfill the high metabolic demands of the proliferating tumor cells exposed to stressful conditions, such as nutrient deprivation, oxidative stress, hypoxia, or in response to therapy [46, 48].…”

“…In this sense, there are a variety of examples showing that autophagy inhibitors, when used in combination with anticancer drugs, may sensitize chemoresistant cells, thus inhibiting tumor survival [47, 71]. For example, it has been reported that inhibition of autophagy function by depletion of Atg5, Atg7 or beclin1 may revert the acquired resistance against tamoxifen in HER-positive breast cancer cells [72].…”

Starvation‐induced autophagy promotes the invasion and migration of human bladder cancer cells via TGF‐β1/Smad3‐mediated epithelial‐mesenchymal transition activation

“…7,8 Autophagy is a highly conserved physiological process that results in the turnover of intracellular material, allowing the cells to remain stable under the stimuli of some stress factors. 10 However, the role and underlying mechanisms of starvation-induced autophagy in the invasion and migration of urinary bladder cancer cells are largely unknown. 10 However, the role and underlying mechanisms of starvation-induced autophagy in the invasion and migration of urinary bladder cancer cells are largely unknown.…”