Regulation ofMYCgene expression by aberrant Wnt/β-catenin signaling in colorectal cancer

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.

Bile acid: a potential inducer of colon cancer stem cells

“…These increases were also accompanied by a 12-fold to 15-fold increase in the level of c-Myc (Fig. 5d), one of the downstream effectors protein of Wnt/β-catenin signaling [47–49]. c-Myc also regulates stemness in CSCs [31].…”

Protective role of +294 T/C (rs2016520) polymorphism of PPARD in Mexican patients with colorectal cancer

“…Recently, several studies have reported that PPARD is upregulated in human colorectal adenomas and cancers (Chen et al, 2004;Takami et al, 2007;Dong et al, 2009;Peters et al, 2011;Rennoll and Yochum, 2015). Barak et al (2002) observed a non-statistically significant but reduced expression of PPARD and a decreased incidence of intestinal tumorigenesis in a knockout APC deleted mouse model (Hu et al, 2006).…”

“…TCF7L2 forms a protein complex with the lymphoid factor 1. Interaction of LEF/TCF with the β-catenin protein results in the formation of a transcription complex that regulates the expression of target genes participating in colorectal carcinogenesis, such as CCND1, PPARD, and c-Myc (He et al, 1999;Krausova and Korinek, 2014;Rennoll and Yochum, 2015). He et al (1999) identified the peroxisome proliferator-activated receptor δ (PPARD) gene as a target of APC through the analysis of global gene expression profiles in human colorectal cancer cell lines (He et al, 1999).…”

LMO2 attenuates tumor growth by targeting the Wnt signaling pathway in breast and colorectal cancer

“…This leads to the accumulation and nuclear translocation of β-catenin, where it functions a co-activator of the transcription factor TCF/LEF1516. The Wnt signaling pathway is also responsible for tumor development, particularly in cancers of the digestive system, including hepatocellular, pancreatic, gastric and colorectal cancers17181920. Moreover, Wnt signaling also plays pivotal roles in the tumorigenesis of some other tissue-derived cancers, such as breast cancer and melanoma2122.…”