ArticlePloS one2015
Hepatitis B Virus Pre-S2 Mutant Induces Aerobic Glycolysis through Mammalian Target of Rapamycin Signal Cascade.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- A Systematic Review of the Impact of Resveratrol on Viral Hepatitis and Chronic Viral Hepatitis-related Hepatocellular Carcinoma.Current molecular medicine · 2025Pooled it
- ChIP-seq and RNA-seq Reveal the Involvement of Histone Lactylation Modification in Early Pregnancy with Subclinical Hypothyroidism.Biochemical genetics · 2026Article
- HBV and host metabolic crosstalk: Reprogramming pathways for viral replication and pathogenesis.Virologica Sinica · 2025Review
- Article
- Stimulation of neutral lipid synthesis via viral growth factor signaling and ATP citrate lyase during vaccinia virus infection.Journal of virology · 2024Article
- Inhibition of GLUD1 mediated by LASP1 and SYVN1 contributes to hepatitis B virus X protein-induced hepatocarcinogenesis.Journal of molecular cell biology · 2024Article
- Article
- Microbiota and Immunity during Respiratory Infections: Lung and Gut Affair.International journal of molecular sciences · 2024Review
- mTOR Signaling: Roles in Hepatitis B Virus Infection and Hepatocellular Carcinoma.International journal of biological sciences · 2024Review
- Review
- Article
- Dissecting the roles and clinical potential of YY1 in the tumor microenvironment.Frontiers in oncology · 2023Review
- Review
- Cellular Senescence in Immunity against Infections.International journal of molecular sciences · 2022Review
- Article
- Solute carrier family 2 members 1 and 2 as prognostic biomarkers in hepatocellular carcinoma associated with immune infiltration.World journal of clinical cases · 2022Article
- Review
- What role for cellular metabolism in the control of hepatitis viruses?Frontiers in immunology · 2022Review
- The Role of Metabolic Dysfunction in T-Cell Exhaustion During Chronic Viral Infection.Frontiers in immunology · 2022Review
- mTOR Signaling: The Interface Linking Cellular Metabolism and Hepatitis B Virus Replication.Virologica Sinica · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis B virus (HBV) pre-S2 mutant can induce hepatocellular carcinoma (HCC) via the induction of endoplasmic reticulum stress to activate mammalian target of rapamycin (MTOR) signaling. The association of metabolic syndrome with HBV-related HCC raises the possibility that pre-S2 mutant-induced MTOR activation may drive the development of metabolic disorders to promote tumorigenesis in chronic HBV infection. To address this issue, glucose metabolism and gene expression profiles were analyzed in transgenic mice livers harboring pre-S2 mutant and in an in vitro culture system. The pre-S2 mutant transgenic HCCs showed glycogen depletion. The pre-S2 mutant initiated an MTOR-dependent glycolytic pathway, involving the eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), Yin Yang 1 (YY1), and myelocytomatosis oncogene (MYC) to activate the solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1), contributing to aberrant glucose uptake and lactate production at the advanced stage of pre-S2 mutant transgenic tumorigenesis. Such a glycolysis-associated MTOR signal cascade was validated in human HBV-related HCC tissues and shown to mediate the inhibitory effect of a model of combined resveratrol and silymarin product on tumor growth. Our results provide the mechanism of pre-S2 mutant-induced MTOR activation in the metabolic switch in HBV tumorigenesis. Chemoprevention can be designed along this line to prevent HCC development in high-risk HBV carriers.
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