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Updated: Oct 28, 2025

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties
Shudong Zhu1,2,3, Yan Zhu1,3, Qiuwen Wang2
1School of Medicine, Nantong University, Nantong, China.
Abstract:
Src is an important oncogene that plays key roles in multiple signal transduction pathways. Csk-homologous kinase (CHK) is a kinase whose molecular roles are largely uncharacterized. We previously reported expression of CHK in normal human colon cells, and decreased levels of CHK protein in colon cancer cells leads to the activation of Src (Zhu et al., 2008). However, how CHK protein expression is downregulated in colon cancer cells has been unknown. We report herein that CHK mRNA was decreased in colon cancer cells as compared to normal colon cells, and similarly in human tissues of normal colon and colon cancer. Increased levels of DNA methylation at promotor CpG islands of CHK gene were observed in colon cancer cells and human colon cancer tissues as compared to their normal healthy counterparts. Increased levels of DNA methyltransferases (DNMTs) were also observed in colon cancer cells and tissues. DNA methylation and decreased expression of CHK mRNA were inhibited by DNMT inhibitor 5-Aza-CdR. Cell proliferation, colony growth, wound healing, and Matrigel invasion were all decreased in the presence of 5-Aza-CdR. These results suggest that increased levels of DNA methylation, possibly induced by enhanced levels of DNMT, leads to decreased expression of CHK mRNA and CHK protein, promoting increased oncogenic properties in colon cancer cells.
Insights
Decreased Csk-homologous kinase (CHK) in colon cancer is due to DNA methylation, which activates the oncogene Src. Inhibiting DNA methylation with 5-Aza-CdR reduced cancer cell growth and invasion.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Src is a key oncogene in cell signaling.
- Csk-homologous kinase (CHK) normally suppresses Src activity.
- Reduced CHK levels correlate with Src activation in colon cancer.
Purpose of the Study:
- To investigate the mechanism of CHK downregulation in colon cancer.
- To explore the role of DNA methylation in CHK gene silencing.
- To assess the impact of CHK downregulation on colon cancer progression.
Main Methods:
- Quantitative analysis of CHK mRNA and protein levels in colon cancer vs. normal cells/tissues.
- DNA methylation analysis of the CHK gene promoter.
- Assessment of DNA methyltransferase (DNMT) expression.
- Treatment with DNMT inhibitor (5-Aza-CdR) and evaluation of its effects on CHK expression and cancer cell behaviors.
Main Results:
- CHK mRNA and protein are significantly decreased in colon cancer cells and tissues.
- Increased DNA methylation at the CHK gene promoter correlates with decreased CHK expression.
- Elevated DNMT levels are observed in colon cancer.
- DNMT inhibition by 5-Aza-CdR restored CHK expression and reduced cell proliferation, colony formation, wound healing, and invasion.
Conclusions:
- Epigenetic silencing via DNA methylation, potentially driven by increased DNMTs, downregulates CHK in colon cancer.
- This CHK downregulation promotes oncogenic properties, including proliferation and invasion.
- Targeting DNA methylation may offer a therapeutic strategy for colon cancer.
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