ArticleBiochemical and biophysical research communications2021
Nuclear PTEN and p53 suppress stress-induced liver cancer through distinct mechanisms.
Article in Biochemical and biophysical research communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Recent advances of engineered oncolytic viruses-based combination therapy for liver cancer.Journal of translational medicine · 2024Review
- Nuclear PTEN's Functions in Suppressing Tumorigenesis: Implications for Rare Cancers.Biomolecules · 2023Review
- Alkannin exerts antitumor properties in cutaneous squamous cell carcinoma by inducing apoptosis and shifting the M1/M2 polarization of tumor-associated macrophages by upregulating PTEN.The Kaohsiung journal of medical sciences · 2023Article
- Sensitive Electrochemical Biosensor for Rapid Screening of Tumor Biomarker TP53 Gene Mutation Hotspot.Biosensors · 2022Article
- Immunofluorescence Detection of Plasma Membranous PTEN in Cultured Cells.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Article
- Generating a new mouse model for nuclear PTEN deficiency by a single K13R mutation.Genes to cells : devoted to molecular & cellular mechanisms · 2021Article
- Nuclear PTEN deficiency and heterozygous PTEN loss have distinct impacts on brain and lymph node size.Biochemical and biophysical research communications · 2021Article
- Evaluation of Radiation Sensitivity Differences in Mouse Liver Tumor Organoids Using CRISPR/Cas9-Mediated Gene Mutation.Technology in cancer research & treatmentArticle
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
PTEN and p53 are highly mutated in many cancers. These two tumor suppressors have critical functions in the nucleus, such as DNA repair, cell cycle progression, and genome maintenance. However, the in vivo functional relationship of nuclear PTEN and p53 is unknown. Here, we analyzed the liver of mice in which nuclear PTEN and p53 are individually or simultaneously depleted. We found that nuclear PTEN loss greatly upregulates p53 expression upon oxidative stress, while the loss of p53 potentiates stress-induced accumulation of PTEN in the nucleus. Next, we examined oxidative stress-induced DNA damage in hepatocytes, and found that nuclear PTEN loss aggravated the damage while p53 loss did not. Notably, mice lacking nuclear PTEN had increased hepatocellular carcinoma under oxidative stress, while mice lacking p53 in hepatocytes had accelerated hepatocellular carcinoma and intrahepatic cholangiocarcinoma. The formation of cholangiocarcinoma appears to involve the transformation of hepatocytes into cholangiocarcinoma. Simultaneous loss of nuclear PTEN and p53 exacerbated both types of liver cancers. These data suggest that nuclear PTEN and p53 suppress liver cancers through distinct mechanisms.
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