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TPP1 Inhibits DNA Damage Response and Chemosensitivity in Esophageal Cancer
Jilin Wen1, Xiaowu Zhong2, Chuanli Gao1
1Department of Laboratory Medicine, North Sichuan Medical College, Nanchong 637000, China.
Critical Reviews in Eukaryotic Gene Expression
|August 22, 2023
Summary
TPP1 protein is upregulated in esophageal cancer, promoting cancer cell growth and DNA damage resistance. Inhibiting TPP1 may enhance chemotherapy effectiveness by targeting the ATM/ATR-p53 pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Telomere Protective Protein 1 (TPP1) maintains telomere stability.
- TPP1's role in esophageal cancer (EC) is not well understood.
Purpose of the Study:
- To investigate the function of TPP1 in esophageal cancer.
- To explore TPP1's impact on cell proliferation, DNA damage, and chemoresistance.
Main Methods:
- TPP1 knockdown and overexpression in EC cells.
- Flow cytometry, β-galactosidase staining, and Western blotting for DNA damage markers (γ-H2AXS139) and ATM/ATR pathway proteins.
- In vivo tumor xenograft models and chemosensitivity assays with cisplatin.
Main Results:
- TPP1 is upregulated in EC.
- TPP1 knockdown inhibits proliferation, induces G1 arrest, increases DNA damage, and upregulates ATM/ATR pathway proteins.
- TPP1 overexpression reverses these effects.
- TPP1 knockdown inhibits tumor growth in vivo, while overexpression promotes it.
- TPP1 reduces chemosensitivity to cisplatin, suggesting a role in chemoresistance.
Conclusions:
- TPP1 regulates the DNA damage response via the ATM/ATR-p53 pathway in EC.
- TPP1 influences chemoresistance in esophageal cancer.
- TPP1 represents a potential therapeutic target for improving chemotherapy efficacy in EC.
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