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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Role of autophagy in gastric carcinogenesis
Apostolis Papaefthymiou, Gregory Christodoulidis, Apostolos Koffas, Michael Doulberis, Stergios A Polyzos, Anastasios Manolakis, Spyros Potamianos, Andreas Kapsoritakis, Jannis Kountouras
Apostolis Papaefthymiou, Apostolos Koffas, Anastasios Manolakis, Spyros Potamianos, Andreas Kapsoritakis, Department of Gastroenterology, University Hospital of Larissa, Larissa 41110, Thessaly, Greece
Apostolis Papaefthymiou, Michael Doulberis, Stergios A Polyzos, First Laboratory of Pharmacology, Aristotle University of Thessaloniki, Thessaloniki 54124, Macedonia, Greece
Apostolis Papaefthymiou, Michael Doulberis, Jannis Kountouras, Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki 54642, Macedonia, Greece
Gregory Christodoulidis, Department of Surgery, University Hospital of Larissa, Larissa 41110, Thessaly, Greece
Michael Doulberis, Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, Aarau 5001, Switzerland
Author contributions: Papaefthymiou A and Kountouras J conceived the idea and designed and wrote the manuscript; Koffas A and Doulberis M critically revised and edited the manuscript; Christodoulidis G, Polyzos SA, Manolakis A, Potamianos S and Kapsoritakis A critically revised the manuscript; All authors approved the final version
Conflict-of-interest statement: The 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: Apostolis Papaefthymiou, MD, PhD, Resident Gastroenterologist, Department of Gastroenterology, University Hospital of Larissa, Mezourlo, Larissa 41110, Thessaly, Greece. appapaef@hotmail.com
Received: February 16, 2021
Peer-review started: February 16, 2021
First decision: March 29, 2021
Revised: April 6, 2021
Accepted: August 2, 2021
Article in press: August 2, 2021
Published online: October 15, 2021
Gastric cancer represents a common and highly fatal malignancy, and thus a pathophysiology-based reconsideration is necessary, given the absence of efficient therapeutic regimens. In this regard, emerging data reveal a significant role of autophagy in gastric oncogenesis, progression, metastasis and chemoresistance. Although autophagy comprises a normal primordial process, ensuring cellular homeostasis under energy depletion and stress conditions, alterations at any stage of the complex regulatory system could stimulate a tumorigenic and promoting cascade. Among others, Helicobacter pylori infection induces a variety of signaling molecules modifying autophagy, during acute infection or after chronic autophagy degeneration. Subsequently, defective autophagy allows malignant transformation and upon cancer establishment, an overactive autophagy is stimulated. This overexpressed autophagy provides energy supplies and resistance mechanisms to gastric cancer cells against hosts defenses and anticancer treatment. This review interprets the implicated autophagic pathways in normal cells and in gastric cancer to illuminate the potential preventive, therapeutic and prognostic benefits of understanding and intervening autophagy.
Core Tip: Autophagy comprises a substantial normal cellular function, implicated in benign and malignant diseases. Its complex regulatory system can be affected at any stage by endogenous and environmental factors. Helicobacter pylori expresses and stimulates a wide range of autophagy modulators, thus promoting or inhibiting autophagy to yield a survival benefit and cause damage. Concerning gastric cancer, the dysregulated autophagic process facilitates tumor generation, progress and resistance to chemotherapy, through various mechanisms. The current review attempts to decrypt and simplify those mechanisms and the respective pathways, to explain their promising potential for the development of therapeutic agents and prognostic tools.
