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dCTP pyrophosphohydrase exhibits nucleic accumulation in multiple carcinomas
Abstract:
Nucleoside triphosphate pyrophosphohydrolase (NTP-PPase) functions as one of the mechanisms to guarantee the fidelity of DNA replication through the cleavage of non-canonical nucleotides into di- or monophosphates. Human NTP-PPase is poorly understood and investigated. In the present study, by using tissue microassays with the paired cancer and adjacent regions, we found that with the prevalent expression of dCTP pyrophosphohydrase (DCTPP1) in the cytosol and nucleus in tumors investigated, DCTPP1 was inclined to accumulate in the nucleus of cancer cells compared to the paired adjacent tissue cells in multiple carcinoma including lung, breast, liver, cervical, gastric and esophagus cancer. More significantly, the higher DCTPP1 expression in the nucleus of lung, gastric and esophagus cancer cells was associated with histological subtypes. The nucleic accumulation of DCTPP1 was apparently observed as well when cancer cell line MCF-7 was treated with H2O2 in vitro. Considering the roles of DCTPP1 on restricting the concentration of non-canonical nucleotides in the nucleotide pool, accumulation of DCTPP1 in the nucleus of cancer cells might suffice for maintaining the proper DNA replication in order to fulfill the requirement for the survival and proliferation of tumor cells.
Insights
Nucleoside triphosphate pyrophosphohydrolase (NTP-PPase), specifically DCTPP1, accumulates in cancer cell nuclei, potentially aiding tumor survival and proliferation by ensuring accurate DNA replication.
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- Nucleoside triphosphate pyrophosphohydrolase (NTP-PPase) enzymes are crucial for DNA replication fidelity by hydrolyzing non-canonical nucleotides.
- Human NTP-PPase, particularly dCTP pyrophosphohydrolase 1 (DCTPP1), remains under-investigated, especially in the context of cancer.
Purpose of the Study:
- To investigate the expression and localization of DCTPP1 in various human cancers.
- To explore the potential role of DCTPP1 nuclear accumulation in cancer cell survival and proliferation.
Main Methods:
- Tissue microassays comparing paired tumor and adjacent normal tissues from multiple cancer types (lung, breast, liver, cervical, gastric, esophagus).
- In vitro experiments using the MCF-7 cancer cell line treated with hydrogen peroxide (H2O2).
Main Results:
- DCTPP1 is widely expressed in both cytosol and nucleus of tumor cells across investigated carcinomas.
- DCTPP1 shows increased nuclear accumulation in cancer cells compared to adjacent normal cells.
- Higher nuclear DCTPP1 levels correlate with specific histological subtypes in lung, gastric, and esophageal cancers.
- H2O2 treatment induced nuclear accumulation of DCTPP1 in MCF-7 cells.
Conclusions:
- Nuclear accumulation of DCTPP1 in cancer cells may be a mechanism to maintain DNA replication accuracy.
- This nuclear localization could support tumor cell survival and proliferation by managing the nucleotide pool.
- DCTPP1 warrants further investigation as a potential factor in cancer progression.
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