ArticleHepatology (Baltimore, Md.)2019
Dual Roles of Mammalian Target of Rapamycin in Regulating Liver Injury and Tumorigenesis in Autophagy-Defective Mouse Liver.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
- DDX17-mediated raptor-dependent mTORC1 activation links autophagy inhibition and metabolic compensation in HCC development.Cellular & molecular biology letters · 2026Article
- Sexual Dimorphism in the Initial Apoptotic Switch During MASH Progression in Mice.International journal of molecular sciences · 2026Article
- Overexpression miR-125a-5p inhibits HSCs activation and alleviates liver fibrosis through TGF-β/Smad2/3 signaling pathway and autophagy.Cell death discovery · 2025Article
- Guts for Self-Eating: Role of Autophagy in Gastrointestinal Health and Disease.Gastro hep advances · 2025Review
- Autophagy related 14 protects against liver injury by inhibiting multiple cell death pathways.eGastroenterology · 2025Article
- Autophagy: Regulator of cell death.Cell death & disease · 2023Review
- SQSTM1/p62 and Hepatic Mallory-Denk Body Formation in Alcohol-Associated Liver Disease.The American journal of pathology · 2023Review
- Lycopene improves autophagy and attenuates carbon tetrachloride-induced hepatic fibrosis in rats.Croatian medical journal · 2023Article
- Loss of Ufl1/Ufbp1 in hepatocytes promotes liver pathological damage and carcinogenesis through activating mTOR signaling.Journal of experimental & clinical cancer research : CR · 2023Article
- Autologous blood transfusion promotes autophagy and inhibits hepatocellular carcinoma progression through HIF-1α signalling pathway.Journal of cellular and molecular medicine · 2023Article
- Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy.Biomedicines · 2023Review
- Molecular mechanisms of autophagy and implications in liver diseases.Liver research (Beijing, China) · 2023Review
- The Role of Traditional Chinese Medicine Natural Products in β-Amyloid Deposition and Tau Protein Hyperphosphorylation in Alzheimer's Disease.Drug design, development and therapy · 2023Review
- Role of mechanistic target of rapamycin in autophagy and alcohol-associated liver disease.American journal of physiology. Cell physiology · 2022Review
- Article
- Celastrol enhances transcription factor EB (TFEB)-mediated autophagy and mitigates Tau pathology: Implications for Alzheimer's disease therapy.Acta pharmaceutica Sinica. B · 2022Article
- Linking of Senescence to Autophagy Deficiency in Chronic Liver Disease.Cellular and molecular gastroenterology and hepatology · 2022Article
- mTOR regulates aerobic glycolysis through NEAT1 and nuclear paraspeckle-mediated mechanism in hepatocellular carcinoma.Theranostics · 2022Article
- Scramblases as Regulators of Autophagy and Lipid Homeostasis: Implications for NAFLD.Autophagy reports · 2022Article
- Dual roles of p62/SQSTM1 in the injury and recovery phases of acetaminophen-induced liver injury in mice.Acta pharmaceutica Sinica. B · 2021Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Autophagy is a lysosomal degradation pathway that degrades cytoplasmic proteins and organelles. Absence of autophagy in hepatocytes has been linked to promoting liver injury and tumorigenesis; however, the mechanisms behind why a lack of autophagy induces these complications are not fully understood. The role of mammalian target of rapamycin (mTOR) in impaired autophagy-induced liver pathogenesis and tumorigenesis was investigated by using liver-specific autophagy related 5 knockout (L-ATG5 KO) mice, L-ATG5/mTOR, and L-ATG5/Raptor double knockout (DKO) mice. We found that deletion of mTOR or Raptor in L-ATG5 KO mice at 2 months of age attenuated hepatomegaly, cell death, and inflammation but not fibrosis. Surprisingly, at 6 months of age, L-ATG5/mTOR DKO and L-ATG5/Raptor DKO mice also had increased hepatic inflammation, fibrosis, and liver injury, similar to the L-ATG5 KO mice. Moreover, more than 50% of L-ATG5/mTOR DKO and L-ATG5/Raptor DKO mice already developed spontaneous tumors, but none of the L-ATG5 KO mice had developed any tumors at 6 months of age. At 9 months of age, all L-ATG5/mTOR DKO and L-ATG5/Raptor DKO had developed liver tumors. Mechanistically, L-ATG5/mTOR DKO and L-ATG5/Raptor DKO mice had decreased levels of hepatic ubiquitinated proteins and persistent nuclear erythroid 2 p45-related factor 2 activation but had increased Akt activation compared with L-ATG5 KO mice. Conclusion: Loss of mTOR signaling attenuates the liver pathogenesis in mice with impaired hepatic autophagy but paradoxically promotes tumorigenesis in mice at a relatively young age. Therefore, the balance of mTOR is critical in regulating the liver pathogenesis and tumorigenesis in mice with impaired hepatic autophagy.
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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.