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Potential Dual Role of Activating Transcription Factor 3 in Colorectal Cancer
Xiaojing Jiang1, Kui-Jin Kim1, Taekyu Ha1
1Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD, U.S.A.
Background/Aim:
Activating transcription factor 3 (ATF3) is a member of the ATF/CREB transcription factor family and has been proposed as a molecular target for cancer therapy. The present study was undertaken in order to investigate whether ATF3 influences cancer-related phenotypes in colorectal cancer.
Materials And Methods:
ATF3 was overexpressed in human colorectal cancer cells and the effects of ATF3 on apoptosis, cell cycle, cell migration and epithelial mesenchymal transition (EMT) were investigated. B-cell lymphoma-2 (Bcl-2) promoter was cloned and used for luciferase assay in cells transfected with control or ATF3 expression vector.
Results:
ATF3 down-regulated the expression of Bcl-2 and promoter activity of the Bcl-2 gene. ATF3 increased collective cell migration and expression of cluster of differentiation 44 (CD44) and decreased retinoblastoma (Rb) expression. In addition, ATF3 down-regulated EMT-inducing transcription factors and β-catenin.
Conclusion:
ATF3 may play a dichotomous role in apoptosis and metastasis in human colorectal cancer cells.
Insights
Activating transcription factor 3 (ATF3) impacts colorectal cancer cell phenotypes. ATF3 influences apoptosis, cell migration, and epithelial mesenchymal transition (EMT), suggesting a dual role in cancer progression.
Area of Science:
- Molecular biology
- Cancer research
- Genetics
Background:
- Activating transcription factor 3 (ATF3) is part of the ATF/CREB transcription factor family.
- ATF3 is a potential molecular target for cancer therapy.
Purpose of the Study:
- Investigate the influence of ATF3 on cancer-related phenotypes in colorectal cancer.
- Determine ATF3's role in apoptosis, cell cycle, cell migration, and epithelial mesenchymal transition (EMT).
Main Methods:
- Overexpression of ATF3 in human colorectal cancer cells.
- Assessed effects on apoptosis, cell cycle, migration, and EMT.
- Utilized luciferase assay to evaluate Bcl-2 promoter activity.
Main Results:
- ATF3 downregulated B-cell lymphoma-2 (Bcl-2) expression and promoter activity.
- ATF3 enhanced collective cell migration and cluster of differentiation 44 (CD44) expression.
- ATF3 decreased retinoblastoma (Rb) expression, EMT-inducing transcription factors, and β-catenin.
Conclusions:
- ATF3 exhibits a dichotomous role in colorectal cancer.
- ATF3 influences both apoptosis and metastasis in human colorectal cancer cells.
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