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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2021; 13(6): 542-567
Published online Jun 26, 2021. doi: 10.4252/wjsc.v13.i6.542
Epigenetic regulation of autophagy: A key modification in cancer cells and cancer stem cells
Harpreet K Mandhair, Urban Novak, Ramin Radpour
Harpreet K Mandhair, Urban Novak, Ramin Radpour, Department for BioMedical Research, University of Bern, Bern 3008, Switzerland
Harpreet K Mandhair, Urban Novak, Ramin Radpour, Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern 3008, Switzerland
Author contributions: Mandhair HK, Novak U and Radpour R wrote the paper; Novak U and Radpour R are co-senior authors.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ramin Radpour, MSc, PhD, Lecturer, Senior Scientist, Department for BioMedical Research, University of Bern, Murtenstrasse 35, Bern 3008, Switzerland. ramin.radpour@dbmr.unibe.ch
Received: February 25, 2021
Peer-review started: February 25, 2021
First decision: April 20, 2021
Revised: May 2, 2021
Accepted: June 4, 2021
Article in press: June 4, 2021
Published online: June 26, 2021
Abstract

Aberrant epigenetic alterations play a decisive role in cancer initiation and propagation via the regulation of key tumor suppressor genes and oncogenes or by modulation of essential signaling pathways. Autophagy is a highly regulated mechanism required for the recycling and degradation of surplus and damaged cytoplasmic constituents in a lysosome dependent manner. In cancer, autophagy has a divergent role. For instance, autophagy elicits tumor promoting functions by facilitating metabolic adaption and plasticity in cancer stem cells (CSCs) and cancer cells. Moreover, autophagy exerts pro-survival mechanisms to these cancerous cells by influencing survival, dormancy, immunosurveillance, invasion, metastasis, and resistance to anti-cancer therapies. In addition, recent studies have demonstrated that various tumor suppressor genes and oncogenes involved in autophagy, are tightly regulated via different epigenetic modifications, such as DNA methylation, histone modifications and non-coding RNAs. The impact of epigenetic regulation of autophagy in cancer cells and CSCs is not well-understood. Therefore, uncovering the complex mechanism of epigenetic regulation of autophagy provides an opportunity to improve and discover novel cancer therapeutics. Subsequently, this would aid in improving clinical outcome for cancer patients. In this review, we provide a comprehensive overview of the existing knowledge available on epigenetic regulation of autophagy and its importance in the maintenance and homeostasis of CSCs and cancer cells.

Keywords: Autophagy, Cancer stem cells, Cancer cells, Epigenetics, Histone remodeling, DNA methylation, Non-coding RNA

Core Tip: Cancer stem cells are a distinct population in the tumor bulk with enhanced self-renewal capability. Autophagy primarily exerts oncogenic activity and adaptive signals during cancer progression. Similarly, epigenetic modifications display a crucial role in tumor initiation and cancer development through its regulation of tumor suppressor genes and oncogenes. Emerging studies report epigenetic modifications regulate autophagy and metabolic pathways promoting tumor growth, elicit immunosuppressive activity and contribute to therapy resistance. Therefore, understanding this complex signaling patterns can theoretically lead to a more efficient and targeted cancer treatment.