Assessing the activity of the MYC-EGR1 pathway in p53-variant human colorectal cancer cells

Publication Date

2026

College

College of Sciences & Mathematics

Department

Biology, Department of

Faculty Mentor

Erick Spears

Presentation Type

Talk/Oral

Summary

The Wnt signaling pathway regulates the proliferation of intestinal epithelial cells and maintains the cell in an undifferentiated state. Dysregulation of Wnt signaling leads to uncontrolled proliferation and thus contributes to colorectal cancer growth, primarily through increased expression of the Wnt target gene MYC. While MYC is classically known to promote proliferation, previous studies in mouse embryonic fibroblasts cells have shown that, in the absence of functional p53, MYC can upregulate the tumor suppressor gene EGR1, leading to apoptosis rather than proliferation. This MYC-EGR1 pathway has not yet been demonstrated in human colorectal cancer cells, despite the frequent loss of p53 in late-stage colorectal cancer. To determine whether the MYC-EGR1 pathway is present in human intestinal epithelial cells, variant HCT116 colorectal cancer cell lines with either wild-type p53 (p53+/+) or a knockout of the TP53 locus (p53-/-) were studied. Quantitative real-time RT-PCR (qRT-PCR) analysis was used to assess MYC and EGR1 mRNA levels in these p53-variant cell lines and indicated slightly higher EGR1 expression in the p53-/- cells. To assess whether MYC is impacting EGR1 expression, particularly in the p53-/- cells, they will be transduced with MYC-specific shRNA to decrease its expression. Transduction efficiency of the targeted shRNA will be calculated by visualizing a GFP co-transduction marker. Analysis of mRNA by qRT-PCR will evaluate whether decreasing MYC expression in these cells also decreases EGR1 expression in a p53-dependent manner. Both cell lines will be evaluated for TP53 expression to validate that p53 is lost form the p53-/- cells.  These studies will contribute to our understanding of the role of MYC in proliferation of intestinal epithelium and the mechanisms by which it contributes to colorectal malignancy. The identification of the MYC-EGR1 pathway in human colorectal cancer cells, particularly those that lack p53, may reveal a novel therapeutic target for late-stage disease.

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