ArticleScience signaling2012
Chronic activation of mTOR complex 1 is sufficient to cause hepatocellular carcinoma in mice.
Article in Science signaling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
111 citing papers in PubMed, 179 citations in OpenAlex.
- Regulation of Amino Acid Transporters and Sensors in Response to a High protein Diet: A Randomized Controlled Trial in Elderly Men.The journal of nutrition, health & aging · 2019Trial
- Noncanonical mTORC1-TFEB activation promotes hepatocyte plasticity and high-grade malignancy in hepatocellular carcinoma.The Journal of clinical investigation · 2026Article
- mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation.Science advances · 2026Article
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Adaptive oncogenesis of β-catenin emerges from declining liver tissue integrity.Nature communications · 2026Article
- A method utilizing chemical carcinogens and a Western diet to reliably induce advanced hepatocellular carcinoma in male and female mice.Cancer & metabolism · 2026Article
- COVID-19 and Congenital Cleft Lip and Palate: A Systematic Review Focusing on Nonsyndromic Neonatal Outcomes.Cureus · 2026Review
- Targeting mTORC2-dependent AKT/FOXO1/RNF125 signaling exploits a therapeutic vulnerability in c-MET-activated and β-catenin-mutated hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2025Article
- AKT-mediated phosphorylation of TSC2 controls stimulus- and tissue-specific mTORC1 signaling and organ growth.Developmental cell · 2025Article
- Folliculin depletion results in liver cell damage and cholangiocarcinoma through MiT/TFE activation.Cell death and differentiation · 2025Article
- S-adenosylmethionine deficit disrupts very low-density lipoprotein metabolism promoting liver lipid accumulation in mice.Journal of lipid research · 2025Article
- Metabolic reprogramming in hepatocellular carcinoma: mechanisms and therapeutic implications.Experimental & molecular medicine · 2025Review
- Ammonium metabolism rewiring in the prostate cancer microenvironment: Mechanisms and clinical prospects.Frontiers in oncology · 2025Review
- FBXO22 inhibits colitis and colorectal carcinogenesis by regulating the degradation of the S2448-phosphorylated form of mTOR.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
- Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver.Nature communications · 2024Article
- mTOR Signaling: Roles in Hepatitis B Virus Infection and Hepatocellular Carcinoma.International journal of biological sciences · 2024Review
- Targeting EGFR/PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma.Pharmaceutics · 2023Review
- Signaling Pathways Leading to mTOR Activation Downstream Cytokine Receptors in Lymphocytes in Health and Disease.International journal of molecular sciences · 2023Review
- The Role of mTOR Inhibitors after Liver Transplantation for Hepatocellular Carcinoma.Current oncology (Toronto, Ont.) · 2023Review
51 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a nutrient-sensitive protein kinase that is aberrantly activated in many human cancers. Whether dysregulation of mTORC1 signaling in normal tissues increases the risk for cancer, however, is unknown. We focused on hepatocellular carcinoma, which has been linked to environmental factors that affect mTORC1 activity, including diet. Ablation of the gene encoding TSC1 (tuberous sclerosis complex 1), which as part of the TSC1-TSC2 complex is an upstream inhibitor of mTORC1, results in constitutively increased mTORC1 signaling, an effect on this pathway similar to that of obesity. We found that mice with liver-specific knockout of Tsc1 developed sporadic hepatocellular carcinoma with heterogeneous histological and biochemical features. The spontaneous development of hepatocellular carcinoma in this mouse model was preceded by a series of pathological changes that accompany the primary etiologies of this cancer in humans, including liver damage, inflammation, necrosis, and regeneration. Chronic mTORC1 signaling led to unresolved endoplasmic reticulum stress and defects in autophagy, factors that contributed to hepatocyte damage and hepatocellular carcinoma development. Therefore, we conclude that increased activation of mTORC1 can promote carcinogenesis and may thus represent a key molecular link between cancer risk and environmental factors, such as diet.
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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.