Reza Sahebi1, Nazanin Akbari2, Zeynab Bayat , Mohammad Rashidmayvan1, Amin Mansoori1, and Maria Beihaghi
Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Biology, Faculty of Sciences, Shahid Beheshti University, Tehran, Iran
Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran Department of Biology, Kavian Institute of Higher Education, Mashhad, Iran
School of Science and Technology, The University of Georgia, Tbilisi, Georgia
# Reza Sahebi and Nazanin Akbari contributed equally to this study.
* Corresponding author: Reza Sahebi, Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Email: email@example.com
Autophagy is a well-known vital process in cells and plays a significant role in biological evolution, the immune system, and cell death. It can be effective in fatal disorders, such as nervous system degeneration, autoimmune diseases, and cancer. Autophagy has a dual role; on the one hand, it increases cell survival, and on the other hand, it causes cell death in advanced stages although no agreement has yet been accomplished on the role of autophagy in cellular processes. There is evidence that autophagic signaling regulation is inversely related to oncogenic signaling. Numerous commonly activated oncogenes (class I PtdIns3K, Akt, TOR, Bcl-2) inhibit autophagy, while commonly mutated or epigenetically silenced tumor suppressor genes (p53, PTEN, TSC1/TSC2) promote autophagy. Autophagy promotes cancer progression by supplying sufficient nutrients that enable cancer cell growth. FIP200, a related- autophagy protein, interacts with ATG 13 and induces autophagy. Increased autophagy causes the interaction of Becklin 118 with HER2, resulting in an increase in tumorigenesis. In order to make complete use of the autophagic properties in cancer treatment, further studies on its role in disease in the different biologics fields are essential. Cancer stem cells (CSCs) can regenerate, cause cancer, and enhance resistance to treatment, metastasis, and recurrence. Autophagy moderates stressful conditions and promotes resistance to anticancer therapy. In addition, autophagy regulates the ability of radiation in CSCs and leads to failure in anticancer therapies. Hence, autophagy is a potential therapeutic target for metastasis resistance and anticancer therapy recurrence. Regulation of autophagy using autophagy modulators alone does not improve the therapeutic effects of anticancer reagents. In contrast, it has supplied nutrients for cancer cells. Consequently, clinical trials aiming for autophagy through a combination of autophagy modulations and anticancer reagents are crucial to consider autophagy as a potentially effective therapeutic strategy in anticancer therapy.
Autophagy as an intracellular process enhances important catabolic and cellular degradation in eukaryotes, which plays a vital role in preserving cellular homeostasis, providing nutritional requirements of cells, and eliminating old and damaged organelle, protein, and other macromolecules1. In fact, autophagy is an induced response in starvation conditions, protecting the amino acid pool against gluconeogenesis and synthesizing essential proteins for survival2. Autophagy consists of several sequential steps. These steps include inducing paths leading to autophagy, selection of organs and proteins that require destruction, nucleation and formation of membranes (phagocytosis), expansion and evolution of autophagy, reconstruction of used components, fusion of lysosomes with autophagic membranes and formation of phagocytosis, and finally, decompositions of cellular components, in which, proteins, such as Atg10 and Beclin1 play an important role (Figure 1).