Autophagy-related signaling pathways are involved in cancer (Review)

Abstract

Autophagy is a self-digestion process in cells that can maintain energy homeostasis under normal circumstances. However, misfolded proteins, damaged mitochondria and other unwanted components in cells can be decomposed and reused via autophagy in some specific cases (including hypoxic stress, low energy states or nutrient deprivation). Therefore, autophagy serves a positive role in cell survival and growth. However, excessive autophagy may lead to apoptosis. Furthermore, abnormal autophagy may lead to carcinogenesis and promote tumorigenesis in normal cells. In tumor cells, autophagy may provide the energy required for excessive proliferation, promote the growth of cancer cells, and evade apoptosis caused by certain treatments, including radiotherapy and chemotherapy, resulting in increased treatment resistance and drug resistance. On the other hand, autophagy leads to an insufficient nutrient supply in cancer cells and the destruction of energy homeostasis, thereby inducing cancer cell apoptosis. Therefore, understanding the mechanism of the double-edged sword of autophagy is crucial for the treatment of cancer. The present review summarizes the signaling pathways and key factors involved in autophagy and cancer to provide possible strategies for treating tumors.

Punicalagin in Cancer Prevention—Via Signaling Pathways Targeting

“…Macroautophagy proceeds through the formation of an autophagosome (a sequestration of a fragment of cytoplasm by surrounding its contents with double membranes) and then its fusion with lysosome (yielding autophagolysosome) to deliver hydrolases required for the degradation of the enclosed molecules [ 54 ]. This process requires five stages: induction, nucleation, autophagosome extension, maturation, and autophagolysis [ 55 , 56 ]. Signaling pathways regulating those events include mammalian target of rapamycin (mTOR), as well as AMP-activated protein kinase (AMPK) routes.…”

“…Therefore, some autophagy-related factors seem to work as tumor suppressors in the incipient neoplasias. An example is beclin-1 (the protein indispensable in the membrane nucleation—phagophore formation stage, as well as autophagosome maturation [ 55 ]) being attenuated in some cancers, such as breast [ 57 , 58 ], ovarian [ 57 , 59 ], prostate [ 57 ], cervical [ 60 ], lung [ 61 ], liver [ 62 , 63 ] cancer, osteosarcoma [ 64 ], and glioblastoma [ 65 ]. However, after the initiation of cancer development, the altered phenotype seems to employ autophagic machinery to survive in unfavorable conditions of the host microenvironment, e.g., under stressful circumstances associated with host immune system response, or starvation and oxygen deprivation, before the formation of new blood vessels after metastasizing to a distant locus.…”

“…For example, whereas Shen et al [ 59 ] observed decreased beclin-1 expression in ovarian cancer, especially in more advanced stages, Cai et al [ 67 ] noted its overexpression correlated positively with the better survival rates. Recent literature data describing autophagy function in cancer development, as well as signal transduction pathways implicated in this process, focused on anticancer therapy (including the assessment of phytotherapeutics) have been addressed in several review papers [ 53 , 55 , 56 , 68 , 69 , 70 ].…”

Steroidal Saponins Isolated from the Rhizome of Dioscorea tokoro Inhibit Cell Growth and Autophagy in Hepatocellular Carcinoma Cells

“…Induction of autophagy may limit tumor development. However, inhibition of autophagy has been observed in mouse models, leading to an enhanced response to anticancer agents through the disruption of tumor defense mechanisms [ 15 , 16 , 17 ]. Therefore, further studies are needed to understand the modulation of autophagy and cancer development.…”

Targeting Autophagy with Natural Compounds in Cancer: A Renewed Perspective from Molecular Mechanisms to Targeted Therapy

“…Autophagy, through its conservative mechanism, decomposes macromolecules and provides a lot of nutrients, so it plays an irreplaceable role in regulating metabolism and cell growth (Yan et al, 2019). Importantly, autophagy has dual effect on cancers, which may protect cancer cells from extreme nutrient conditions, while it also causes destruction of energy homeostasis and kill cancer cells (Chen et al, 2021). In physiological state, autophagy maintains cell homeostasis by degrading and removing damaged or dead organelles, misfolded proteins and other substances, while abnormal autophagy will break the original balance of cells, and even play a key role in the occurrence and development of cancer (Byun et al, 2017).…”