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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2015; 7(11): 271-284
Published online Nov 15, 2015. doi: 10.4251/wjgo.v7.i11.271
Autophagy in colorectal cancer: An important switch from physiology to pathology
Florin Burada, Elena Raluca Nicoli, Marius Eugen Ciurea, Daniel Constantin Uscatu, Mihai Ioana, Dan Ionut Gheonea
Florin Burada, Marius Eugen Ciurea, Mihai Ioana, Dan Ionut Gheonea, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania
Elena Raluca Nicoli, Department of Pharmacology, University of Oxford, Oxford, OX13QT London, United Kingdom
Elena Raluca Nicoli, Daniel Constantin Uscatu, Human Genomics Laboratory, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania
Author contributions: Burada F, Nicoli ER, Ciurea ME and Uscatu DC performed the literature research; Burada F, Nicoli RE and Gheonea DI wrote the paper; Uscatu DC and Ioana M created the Figures; Burada F, Ioana M, Ciurea M and Gheonea DI critically revised the paper.
Supported by Grant POSDRU/159/1.5/S/133377, from European Social Found, Human Resources Development Operational Programme 2007-2013 (to Burada F).
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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:
Correspondence to: Florin Burada, MD, PhD, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 1 Mai 66, 200638 Craiova, Romania.
Telephone: +40-745-683949 Fax: +40-251-593077
Received: May 14, 2015
Peer-review started: May 15, 2015
First decision: June 2, 2015
Revised: June 20, 2015
Accepted: September 30, 2015
Article in press: October 9, 2015
Published online: November 15, 2015

Colorectal cancer (CRC) remains a leading cause of cancer death in both men and women worldwide. Among the factors and mechanisms that are involved in the multifactorial etiology of CRC, autophagy is an important transformational switch that occurs when a cell shifts from normal to malignant. In recent years, multiple hypotheses have been considered regarding the autophagy mechanisms that are involved in cancer. The currently accepted hypothesis is that autophagy has dual and contradictory roles in carcinogenesis, but the precise mechanisms leading to autophagy in cancer are not yet fully defined and seem to be context dependent. Autophagy is a surveillance mechanism used by normal cells that protects them from the transformation to malignancy by removing damaged organelles and aggregated proteins and by reducing reactive oxygen species, mitochondrial abnormalities and DNA damage. However, autophagy also supports tumor formation by promoting access to nutrients that are critical to the metabolism and growth of tumor cells and by inhibiting cellular death and increasing drug resistance. Autophagy studies in CRC have focused on several molecules, mainly microtubule-associated protein 1 light chain 3, beclin 1, and autophagy related 5, with conflicting results. Beneficial effects were observed for some agents that modulate autophagy in CRC either alone or, more often, in combination with other agents. More extensive studies are needed in the future to clarify the roles of autophagy-related genes and modulators in colorectal carcinogenesis, and to develop potential beneficial agents for the prognosis and treatment of CRC.

Keywords: Colorectal cancer, Autophagy, Gene, Protein, Carcinogenesis

Core tip: This review describes the role of autophagy in cancer, focusing on the involvement of autophagy in colorectal cancer (CRC). Initially, we describe the steps and components of autophagy, and we then further highlight the dual role of autophagy in cancer, where it can potentially act as both a promoter and an inhibitor during the transformation from normal to malignant cell. In particular, we emphasize the major autophagy genes involved in CRC pathogenesis along with autophagy-modulating agents and their modes of action in the context of CRC therapy.