Differential mechanisms of autophagy in cancer stem cells: Emphasizing gastrointestinal cancers

Abstract

Gastrointestinal (GI) cancers are one of the most common forms of malignancies and still are the most important cause of cancer‐related mortality worldwide. Autophagy is a conserved catabolic pathway involving lysosomal degradation and recycling of whole cellular components, which is essential for cellular homeostasis. For instance, it acts as a pivotal intracellular quality control and repair mechanism but also implicated in cell reformation during cell differentiation and development. Indeed, GI cancer stem cells (CSCs) are thought to be responsible for tumour initiation, traditional therapies resistance, metastasis and tumour recurrence. Molecular mechanisms of autophagy in normal vs CSCs gain great interest worldwide. Here, we shed light on the role of autophagy in normal stem cells differentiation for embryonic progression and its role in maintaining the activity and self‐renewal capacity of CSCs which offer novel viewpoints on promising cancer therapeutic strategies based on the differential roles of autophagy in CSCs.

Polyethylenimine, an Autophagy-Inducing Platinum-Carbene-Based Drug Carrier with Potent Toxicity towards Glioblastoma Cancer Stem Cells

“…Either through a high level of activation of the autophagic pathway or through inhibition of autophagosome-lysosome fusion, causing their accumulation. Autophagy has been shown to be upregulated and used as a survival and drug resistance mechanism in CSCs which is highly implicated in the maintenance of their “stemness” [ 25 , 56 ], with therapeutics targeting this pathway, thus being of greater interest [ 57 , 58 ].…”

Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

“…Apoptosis is regulated by intracellular and/or extracellular signals; hence, the caspase's activation is considered a potential therapeutic target against human cancer diseases [3]. Autophagy is a major pathway in all eukaryotic cells and is considered as a multistep process in which cytoplasm, intracellular organelles, and proteins are sequestered through the fusion of autophagosomes with lysosomes forming autolysosomes, with ultimate degradation by lysosomal hydrolases, while autophagy has a crucial role as an emerging cell survival process [4].…”

Insight into the role of clathrin‐mediated endocytosis inhibitors in SARS‐CoV‐2 infection

“… 59 Barbadin also affects cellular viability and induces both apoptosis and autophagy in breast cancer cells. 84 , 85 , 86 , 87 , 88 This may give genetic inhibitors more leverage to avoid the anticipated adverse effects of chemical inhibitors. Genetic inhibitors are used to inhibit CME by suppressing the expression of specific endocytic proteins.…”

“…Barbadin, for example, is a selective inhibitor of β ‐arrestin/AP2 interaction, 83 ERK1/2, and cAMP accumulation in human embryonic kidney cells 59 . Barbadin also affects cellular viability and induces both apoptosis and autophagy in breast cancer cells 84‐88 . This may give genetic inhibitors more leverage to avoid the anticipated adverse effects of chemical inhibitors.…”