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The crosstalk between Wnt/β-catenin signaling pathway with DNA damage response and oxidative stress: Implications in
Ansar Karimaian1, Maryam Majidinia2, Hossein Bannazadeh Baghi3
1Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran.
Abstract:
DNA repair is essential for maintaining genomic integrity in cells. The dependence of cancer cell survival on proper DNA repair provides an opportunity to treat defective tumors by DNA damaging agents. Not only Wnt signaling has important functions in controlling gene expression, as well as cell polarity, adhesion and behavior, it also highly interacts with DNA damage response (DDR) in different levels. Furthermore, oxidative stress, which is responsible for majority of DNA lesions, affects Wnt signaling in different ways. A better understanding of the cross-talk between these pathways and events could provide strategies for treatment of cancer cells with deficient DNA repair capacity. As such, we will give a brief overview of the importance of the DNA repair machinery, signaling mechanisms of Wnt/β-catenin pathway, and DDR. We will further review the interactions between Wnt signaling and DDR, and the impact of oxidative stress on Wnt signaling. Finally, Wnt signaling is discussed as a potential treatment strategy for cancer.
Insights
Cancer cells rely on DNA repair, creating treatment opportunities. Understanding Wnt signaling, DNA damage response (DDR), and oxidative stress interactions can reveal new cancer therapies targeting DNA repair deficiencies.
Area of Science:
- Cellular Biology
- Molecular Oncology
- Biochemistry
Background:
- Genomic integrity is maintained by DNA repair mechanisms.
- Cancer cell survival is often dependent on DNA repair pathways.
- Wnt signaling regulates gene expression, cell behavior, and interacts with DNA damage response (DDR).
Purpose of the Study:
- To review the interplay between Wnt signaling and DNA damage response (DDR).
- To explore the impact of oxidative stress on Wnt signaling.
- To discuss Wnt signaling as a potential cancer therapeutic strategy.
Main Methods:
- Literature review of DNA repair, Wnt/β-catenin pathway, and DDR.
- Analysis of cross-talk between Wnt signaling and DDR.
- Examination of oxidative stress effects on Wnt signaling.
Main Results:
- Wnt signaling and DDR are intricately linked.
- Oxidative stress significantly influences Wnt signaling pathways.
- Deficiencies in DNA repair present therapeutic vulnerabilities in cancer.
Conclusions:
- Understanding the Wnt/DDR cross-talk and oxidative stress impact is crucial for cancer treatment.
- Targeting Wnt signaling may offer novel therapeutic strategies for cancers with DNA repair defects.
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