ArticleCell death & disease2018
The extent of liver injury determines hepatocyte fate toward senescence or cancer.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- The effects of splenectomy, platelet-rich plasma (PRP) and concentrated growth factor (CGF) on liver regeneration following major hepatectomy in rats.Scientific reports · 2026Article
- Redefining senescence through hepatocyte fate changes in liver diseases.Trends in endocrinology and metabolism: TEM · 2026Review
- Cell type-specific paradox of autophagy and senescence in MASH: implications for precision hepatology.Frontiers in cell and developmental biology · 2026Article
- The context-dependent effect of cellular senescence: From embryogenesis and wound healing to aging.Ageing research reviews · 2025Review
- CDK4/6 inhibitor PD-0332991 suppresses hepatocarcinogenesis by inducing senescence of hepatic tumor-initiating cells.Journal of advanced research · 2025Article
- Global, regional, and national burden of NASH related liver cancer in adults aged 45 and above: an analysis from the GBD 2021 and forecast to 2050.Frontiers in nutrition · 2025Article
- A p21-ATD mouse model for monitoring and eliminating senescent cells and its application in liver regeneration post injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Cell senescence in liver diseases: pathological mechanism and theranostic opportunity.Nature reviews. Gastroenterology & hepatology · 2024Review
- Cellular Senescence in Acute Liver Injury: What Happens to the Young Liver?Aging and disease · 2024Review
- The Role of Oxidative Stress and Cellular Senescence in the Pathogenesis of Metabolic Associated Fatty Liver Disease and Related Hepatocellular Carcinoma.Antioxidants (Basel, Switzerland) · 2023Review
- Is MG53 a potential therapeutic target for cancer?Frontiers in endocrinology · 2023Review
- Review
- Resident macrophages of the lung and liver: The guardians of our tissues.Frontiers in immunology · 2022Review
- Network Pharmacology-Based Strategy to Investigate the Mechanisms of Lenvatinib in the Treatment of Hepatocellular Carcinoma.Computational intelligence and neuroscience · 2022Article
- Pathology and molecular mechanisms of Schistosoma japonicum-associated liver fibrosis.Frontiers in cellular and infection microbiology · 2022Review
- Autophagy suppresses the formation of hepatocyte-derived cancer-initiating ductular progenitor cells in the liver.Science advances · 2021Article
- High-resolution 3D fluorescent imaging of intact tissues.International journal of cardiology and cardiovascular diseases · 2021Article
- Exploring the Mechanisms of Arsenic Trioxide (Evidence-based complementary and alternative medicine : eCAM · 2021Article
- A Three-Dimensional Imaging Method for the Quantification and Localization of Dynamic Cell Tracking Posttransplantation.Frontiers in cell and developmental biology · 2021Article
- Hepatocellular Senescence: Immunosurveillance and Future Senescence-Induced Therapy in Hepatocellular Carcinoma.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well known that induction of hepatocyte senescence could inhibit the development of hepatocellular carcinoma (HCC). Until now, it is still unclear how the degree of liver injury dictates hepatocyte senescence and carcinogenesis. In this study, we investigated whether the severity of injury determines cell fate decisions between hepatocyte senescence and carcinogenesis. After testing of different degrees of liver injury, we found that hepatocyte senescence is strongly induced in the setting of severe acute liver injury. Longer-term, moderate liver injury, on the contrary did not result into hepatocyte senescence, but led to a significant incidence of HCC instead. In addition, carcinogenesis was significantly reduced by the induction of severe acute injury after chronic moderate liver injury. Meanwhile, immune surveillance, especially the activations of macrophages, was activated after re-induction of senescence by severe acute liver injury. We conclude that severe acute liver injury leads to hepatocyte senescence along with activating immune surveillance and a low incidence of HCC, whereas chronic moderate injury allows hepatocytes to proliferate rather than to enter into senescence, and correlates with a high incidence of HCC. This study improves our understanding in hepatocyte cell fate decisions and suggests a potential clinical strategy to induce senescence to treat HCC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.