Autophagy Regulation by the Translation Machinery and Its Implications in Cancer

Abstract

Various metabolic pathways and molecular processes in the cell act intertwined, and dysregulating the interplay between some of them may lead to cancer. It is only recently that defects in the translation process, i.e., the synthesis of proteins by the ribosome using a messenger (m)RNA as a template and translation factors, have begun to gain strong attention as a cause of autophagy dysregulation with effects in different maladies, including cancer. Autophagy is an evolutionarily conserved catabolic process that degrades cytoplasmic elements in lysosomes. It maintains cellular homeostasis and preserves cell viability under various stress conditions, which is crucial for all eukaryotic cells. In this review, we discuss recent advances shedding light on the crosstalk between the translation and the autophagy machineries and its impact on tumorigenesis. We also summarize how this interaction is being the target for novel therapies to treat cancer.

Lysosomotropic agents including azithromycin, chloroquine and hydroxychloroquine activate the integrated stress response

“…3A, B). Many autophagy inducers require eIF2α phosphorylation as a mandatory step for the ignition of the process 48 . Accordingly, we observed that a knockin mutation that renders eIF2α non-phosphorylatable (due to the replacement of serine in position 51 by an alanine residue: genotype eIF2α S51A/S51A ) strongly inhibited the induction of GFP-LC3 puncta by AZT, CQ, and HCQ ( Fig.…”

Regulation of autophagy by microRNAs in human breast cancer

“…The main objective of autophagy or “self-eating” (Greek meaning) is to break down cytoplasmic components like macromolecules and organelles, in order to sustain cellular metabolism and to ensure cellular homeostasis [ 16 , 38 , 39 ]. Some people described autophagy as a cellular “re-cycling process” that digests old and unwanted substances and turns it into useful nutrients for cellular usage [ 25 ].…”

“…Some people described autophagy as a cellular “re-cycling process” that digests old and unwanted substances and turns it into useful nutrients for cellular usage [ 25 ]. Autophagy is important to avoid the accumulation of harmful substances like precipitated proteins, damaged cellular organelles and oncogenic materials that could pose danger to the cells [ 38 , 39 ]. The failures to eliminate these unnecessary, aged or toxic substances would trigger intracellular inflammation which would generate reactive oxygen species (ROS) and subsequently, these cellular processes would lead to the development of cellular degeneration, apoptosis and carcinogenesis [ 38 – 40 ].…”

“…Macroautophagy is an evolutionarily, highly conserved and common type of autophagy that involves the sequestration of a portion of a cellular organelle to form autophagosome [ 41 ]. Lysosome then fuses with the autophagosome to form autolysosome in which the macromolecules like proteins and organelles to be degraded will be digested within the autolysosome [ 39 ]. Selective macroautophagy is a specific type of autophagy in which selected dysfunctional cellular organelles or substrates will be recognized and selected for autophagy [ 38 ].…”

Vault RNAs: hidden gems in RNA and protein regulation

“…Autophagy is besides apoptosis another catabolic pathway essential in homeostasis of cells [ 125 ]. Both mechanisms are interconnected by several molecular nodes and a close cross-talk exists [ 54 ].…”