Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Nov 26, 2019; 11(11): 920-936
Published online Nov 26, 2019. doi: 10.4252/wjsc.v11.i11.920
Colon cancer stemness as a reversible epigenetic state: Implications for anticancer therapies
Audrey Vincent, Aïcha Ouelkdite-Oumouchal, Mouloud Souidi, Julie Leclerc, Bernadette Neve, Isabelle Van Seuningen
Audrey Vincent, Aïcha Ouelkdite-Oumouchal, Mouloud Souidi, Julie Leclerc, Bernadette Neve, Isabelle Van Seuningen, Lille University, Institut National de la Santé et de la Recherche Médicale, CHU Lille, UMR-S 1172-Jean-Pierre Aubert Research Center, Lille F-59000, France
Julie Leclerc, Department of Biochemistry and Molecular Biology, Lille University Hospital, Lille F-59000, France
Author contributions: Vincent A and Ouelkdite-Oumouchal A equally contributed to this paper with literature review, analysis, and drafting; Neve B contributed to the design of the correlation studies; All authors equally contributed to the critical revision and editing and final approval of the final version.
Supported by "Institut National de la Santé et de la Recherche Médicale"; (Inserm); "Centre National de la Recherche Scientifique" (CNRS); "la Ligue Nationale contre le Cancer" (Committees 59, 60 and 62).
Conflict-of-interest statement: The authors declare no conflicts 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 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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Isabelle Van Seuningen, PhD, Director, Inserm UMR-S 1172-Jean-Pierre Aubert Research Center, Bâtiment Cancer, 1 Rue Michel Polonovski, Lille F-59045, France. isabelle.vanseuningen@inserm.fr
Telephone: +33-320-298867 Fax: +33-320-538562
Received: March 26, 2019
Peer-review started: March 28, 2019
First decision: June 3, 2019
Revised: August 29, 2019
Accepted: September 11, 2019
Article in press: September 11, 2019
Published online: November 26, 2019
Processing time: 224 Days and 20.7 Hours
Abstract

The recent discovery of cancer cell plasticity, i.e. their ability to reprogram into cancer stem cells (CSCs) either naturally or under chemotherapy and/or radiotherapy, has changed, once again, the way we consider cancer treatment. If cancer stemness is a reversible epigenetic state rather than a genetic identity, opportunities will arise for therapeutic strategies that remodel epigenetic landscapes of CSCs. However, the systematic use of DNA methyltransferase and histone deacetylase inhibitors, alone or in combination, in advanced solid tumors including colorectal cancers, regardless of their molecular subtypes, does not seem to be the best strategy. In this review, we first summarize the knowledge researchers have gathered on the epigenetic signatures of CSCs with the difficulty of isolating rare populations of cells. We raise questions about the relevant use of currently available epigenetic inhibitors (epidrugs) while the expression of numerous cancer stem cell markers are often repressed by epigenetic mechanisms. These markers include the three cluster of differentiation CD133, CD44 and CD166 that have been extensively used for the isolation of colon CSCs.and . Finally, we describe current treatment strategies using epidrugs, and we hypothesize that, using correlation tools comparing associations of relevant CSC markers with chromatin modifier expression, we could identify better candidates for epienzyme targeting.

Keywords: Cancer stem cells; Colon cancer; Epigenetics; Chromatin modifying enzymes; CD44; CD133; CD166

Core tip: The recent discovery of cancer cell plasticity, i.e. their ability to reprogram into cancer stem cells either naturally or under chemotherapy and/or radiotherapy, has changed, once again, the way we consider cancer treatment. In this review, we try to understand why current epigenetic treatments have failed to prove their efficacy in solid tumors including colorectal cancer and we hypothesize that, using correlation tools comparing associations of relevant cancer stem cell markers with chromatin modifier expression, we may identify better candidates for epienzyme targeting.