Epigenetic Control of Autophagy in Cancer Cells: A Key Process for Cancer-Related Phenotypes

Abstract

Although autophagy is a well-known and extensively described cell pathway, numerous studies have been recently interested in studying the importance of its regulation at different molecular levels, including the translational and post-translational levels. Therefore, this review focuses on the links between autophagy and epigenetics in cancer and summarizes the. following: (i) how ATG genes are regulated by epigenetics, including DNA methylation and post-translational histone modifications; (ii) how epidrugs are able to modulate autophagy in cancer and to alter cancer-related phenotypes (proliferation, migration, invasion, tumorigenesis, etc.) and; (iii) how epigenetic enzymes can also regulate autophagy at the protein level. One noteable observation was that researchers most often reported conclusions about the regulation of the autophagy flux, following the use of epidrugs, based only on the analysis of LC3B-II form in treated cells. However, it is now widely accepted that an increase in LC3B-II form could be the consequence of an induction of the autophagy flux, as well as a block in the autophagosome-lysosome fusion. Therefore, in our review, all the published results describing a link between epidrugs and autophagy were systematically reanalyzed to determine whether autophagy flux was indeed increased, or inhibited, following the use of these potentially new interesting treatments targeting the autophagy process. Altogether, these recent data strongly support the idea that the determination of autophagy status could be crucial for future anticancer therapies. Indeed, the use of a combination of epidrugs and autophagy inhibitors could be beneficial for some cancer patients, whereas, in other cases, an increase of autophagy, which is frequently observed following the use of epidrugs, could lead to increased autophagy cell death.

Prognostic Correlation of an Autophagy-Related Gene Signature in Patients with Head and Neck Squamous Cell Carcinoma

“…Autophagy plays a multifaceted role in tumor initiation and progression in respect of microenvironment stress, nutritional supplement, and immune status [ 7 , 8 ]. Research suggests that autophagy-related mechanism is an optimistic target for future cancer therapy [ 9 ]; thus, exploring the valuable knowledge of autophagy is in urgent need and can offer huge potential in long term.…”

Vanillic Acid Improves Comorbidity of Cancer and Obesity through STAT3 Regulation in High-Fat-Diet-Induced Obese and B16BL6 Melanoma-Injected Mice

“…The results clearly indicated altered autophagy in melanoma tissues of VA-treated mice. VA increased phosphorylation of MEK and ERK, which participate in the later step of autophagy [ 35 ], along with increased autophagy markers, such as Beclin-1, ATG7, and ATG12, and conversion of LC3-I to LC3-II [ 36 ] ( Figure 5 E).…”

Hyperoxia exposure arrests alveolarization in neonatal rats via PTEN‑induced putative kinase 1‑Parkin and Nip3‑like protein X‑mediated mitophagy disorders

“…4E ). The transformation of LC3B from LC3BI (the free form) to LC3BII (the conjugated form of phosphatidyl ethanolamine) is an important process in the formation of autophagosomes ( 27 ). LC3BII/I expression levels in the model group were significantly elevated compared with the control group at P1, 3, 4 and 7 (P<0.05 or P<0.01; Fig.…”