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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Nov 26, 2015; 6(4): 290-300
Published online Nov 26, 2015. doi: 10.4331/wjbc.v6.i4.290
Regulation of MYC gene expression by aberrant Wnt/β-catenin signaling in colorectal cancer
Sherri Rennoll, Gregory Yochum
Sherri Rennoll, Gregory Yochum, Department of Biochemistry and Molecular Biology, the Pennsylvania State University College of Medicine, Hershey, PA 17033-0850, United States
Author contributions: Rennoll S and Yochum G wrote the paper.
Supported by Institutional funds provided by the Pennsylvania State University College of Medicine.
Conflict-of-interest statement: Authors declare no conflicts of interests for this article.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Gregory Yochum, PhD, Department of Biochemistry and Molecular Biology, the Pennsylvania State University College of Medicine, Mail code H171, PO Box 850, Hershey, PA 17033-0850, United States. gsy3@psu.edu
Telephone: +1-717-5312091 Fax: +1-717-5317072
Received: June 10, 2015
Peer-review started: June 14, 2015
First decision: August 25, 2015
Revised: August 26, 2015
Accepted: October 12, 2015
Article in press: October 13, 2015
Published online: November 26, 2015
Processing time: 166 Days and 7.1 Hours
Abstract

The Wnt/β-catenin signaling pathway controls intestinal homeostasis and mutations in components of this pathway are prevalent in human colorectal cancers (CRCs). These mutations lead to inappropriate expression of genes controlled by Wnt responsive DNA elements (WREs). T-cell factor/Lymphoid enhancer factor transcription factors bind WREs and recruit the β-catenin transcriptional co-activator to activate target gene expression. Deregulated expression of the c-MYC proto-oncogene (MYC) by aberrant Wnt/β-catenin signaling drives colorectal carcinogenesis. In this review, we discuss the current literature pertaining to the identification and characterization of WREs that control oncogenic MYC expression in CRCs. A common theme has emerged whereby these WREs often map distally to the MYC genomic locus and control MYC gene expression through long-range chromatin loops with the MYC proximal promoter. We propose that by determining which of these WREs is critical for CRC pathogenesis, novel strategies can be developed to treat individuals suffering from this disease.

Keywords: Wnt; β-catenin; Chromatin looping; Wnt responsive DNA element; MYC

Core tip: In colon cancer, mutations in components of the Wnt/β-catenin signaling pathway result in inappropriate c-MYC proto-oncogene (MYC) expression. To understand colorectal carcinogenesis requires the identification of Wnt responsive DNA elements (WREs) that control MYC expression in colorectal cancer (CRC). Through efforts to characterize MYC WREs, a model has emerged where several of these WREs appear largely dispensable for intestinal homeostasis, but are instead “hijacked” by oncogenic Wnt/β-catenin signaling to drive CRC. These findings raise the intriguing possibility that these WREs may be targeted therapeutically as an alternative approach to treat individuals afflicted by CRC. In this review, we summarize the literature describing the identification of MYC WREs and discuss how those involved in colorectal carcinogenesis may be targeted to limit progression of CRC.