ArticleJournal of experimental & clinical cancer research : CR2022
Aerobic glycolysis enhances HBx-initiated hepatocellular carcinogenesis via NF-κBp65/HK2 signalling.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 77 citations in OpenAlex.
- Nuciferine Suppresses Inflammatory Hepatocarcinogenesis by Targeting cPLA2-Dependent Arachidonic Acid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- TRMT6-Mediated mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- Functional cure for chronic hepatitis B on hepatocellular carcinoma prevention: Evidence and clinical implications.iLIVER · 2026Review
- NF-κB signaling in hepatocellular carcinoma: Mechanisms of tumor progression, immune evasion, and therapeutic resistance.Translational oncology · 2026Review
- Research progress and therapeutic strategies in hepatocellular carcinoma metabolic reprogramming.Journal of advanced research · 2026Review
- Metformin hydrochloride regulates glycolysis and inhibits PEDV replication by inhibition of PI3K-AKT signaling pathway.Journal of virology · 2026Article
- Aerobic glycolysis-driven lactate accumulation and acidic tumor microenvironment in hepatocellular carcinoma: a vicious cycle promoting tumor progression.Frontiers in pharmacology · 2026Review
- The immunoecology of occult hepatitis B virus infection: genetic remodeling and the immune-mediated microcosm.Frontiers in immunology · 2026Review
- New Insights into the Role of NF-κB in Hepatitis B Virus Infection.International journal of biological sciences · 2026Review
- SWI/SNF Chromatin Remodelling Complex in Hepatic Physiology: Mechanistic Insights Into Development, Homeostasis and Pathogenesis.Journal of cellular and molecular medicine · 2026Review
- Lactylated SPTAN1 Accelerates Hepatocellular Carcinoma Progression by Promoting NOTCH1/HES1 Activation and Immunosuppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial gatekeeper in hepatocellular carcinoma: Unraveling the multifaceted roles of VDAC in metabolic reprogramming, apoptosis evasion and therapeutic innovation (Review).Molecular medicine reports · 2026Review
- Liver-joint axis: Hepatitis B virus as a contributor to rheumatoid arthritis pathogenesis.Virulence · 2025Review
- Advancements in research on the role of the key glycolytic enzyme hexokinase 2 in the regulation of tumor immune evasion (Review).Oncology letters · 2025Review
- The bittersweet link between glucose metabolism, cellular microenvironment and viral infection.Virulence · 2025Review
- SUN5 interacts with TRIM28, enhancing IκBα ubiquitination to promote glycolysis in colorectal cancer cells.Acta biochimica et biophysica Sinica · 2025Article
- An overview of hepatitis B virus in gastric carcinogenesis: from clinical association to molecular mechanisms.Infectious agents and cancer · 2025Review
- Beyond borders: engineering organ-targeted immunotherapies to overcome site-specific barriers in cancer.Drug delivery and translational research · 2025Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAerobic glycolysis has been recognized as one of the growth-promoting metabolic alterations of cancer cells. Emerging evidence indicates that nuclear factor κB (NF-κB) plays significant roles in metabolic adaptation in normal cells and cancer cells. However, whether and how NF-κB regulates metabolic reprogramming in hepatocellular carcinoma (HCC), specifically hepatitis B virus X protein (HBx)-initiated HCC, has not been determined.
methodsA dataset of the HCC cohort from the TCGA database was used to analyse the expression of NF-κB family members. Expression of NF-κBp65 and phosphorylation of NF-κBp65 (p-p65) were detected in liver tissues from HBV-related HCC patients and normal controls. A newly established HBx
resultsNF-κBp65 was upregulated in HBV-related HCC, and HBx induced NF-κBp65 upregulation and phosphorylation in vivo and in vitro. Hepatocyte-specific NF-κBp65 deficiency remarkably decreased HBx-initiated spontaneous HCC incidence in HBx-TG mice. Mechanistically, HBx induced aerobic glycolysis by activating NF-κBp65/hexokinase 2 (HK2) signalling in spontaneous hepatocarcinogenesis, and overproduced lactate significantly promoted HCC cell pernicious proliferation via the PI3K (phosphatidylinositide 3-kinase)/Akt pathway in hepatocarcinogenesis.
conclusionThe data elucidate that NF-κBp65 plays a pivotal role in HBx-initiated spontaneous HCC, which depends on hyperactive NF-κBp65/HK2-mediated aerobic glycolysis to activate PI3K/Akt signalling. Thus, phosphorylation of NF-κBp65 will be a potential therapeutic target for HBV-related 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.