ArticleHepatology (Baltimore, Md.)2018
High mobility group protein B1 controls liver cancer initiation through yes-associated protein -dependent aerobic glycolysis.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 165 citations in OpenAlex.
- HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis.The Journal of clinical investigation · 2018Trial
- Engineering Extracellular Vesicles for Anti-Aging Therapy: Mechanisms, Applications, and Perspectives.Aging cell · 2026Review
- Dual inhibition of glycolysis and glutaminolysis by targeting FOXO3 for hepatocellular carcinoma treatment.Oncogene · 2026Article
- The Patatin-Like Phospholipase Domain-Containing 3 148M Variant Exacerbates Alcohol-Induced Liver Injury and Tumorigenesis in Mice.The American journal of pathology · 2026Article
- HMGB1 couples LEF1 to regulate B cell immunity.JCI insight · 2025Article
- A skin organoid-based infection platform identifies an inhibitor specific for HFMD.Nature communications · 2025Article
- Review
- Mechanism of action of HMGB1 in urologic malignancies.Frontiers in oncology · 2025Review
- Metabolic reprogramming of glucose: the metabolic basis for the occurrence and development of hepatocellular carcinoma.Frontiers in oncology · 2025Review
- Fenvalerate exposure induces AKT/AMPK-dependent alterations in glucose metabolism in hepatoma cells.Frontiers in pharmacology · 2025Article
- YAP/TAZ as master regulators in liver regeneration and disease: insights into mechanisms and therapeutic targets.Molecular biology reports · 2024Review
- Extracellular NCOA4 is a mediator of septic death by activating the AGER-NFKB pathway.Autophagy · 2024Article
- Macroautophagy/autophagy promotes resistance to KRASCancer letters · 2024Article
- Targeting the Hippo/YAP1 signaling pathway in hepatocellular carcinoma: From mechanisms to therapeutic drugs (Review).International journal of oncology · 2024Review
- Cetylpyridinium chloride triggers paraptosis to suppress pancreatic tumor growth via the ERN1-MAP3K5-p38 pathway.iScience · 2024Article
- Gypenoside inhibits gastric cancer proliferation by suppressing glycolysis via the Hippo pathway.Scientific reports · 2024Article
- Exosomal circSIPA1L3-mediated intercellular communication contributes to glucose metabolic reprogramming and progression of triple negative breast cancer.Molecular cancer · 2024Article
- Role of Hippo pathway dysregulation from gastrointestinal premalignant lesions to cancer.Journal of translational medicine · 2024Review
- Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy.Frontiers in immunology · 2024Review
- The multifunctional protein HMGB1: 50 years of discovery.Nature reviews. Immunology · 2023Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Emerging studies have suggested that the Hippo pathway is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the key regulator of the Hippo pathway in liver tumor metabolic reprogramming remains elusive. Here, we provide evidence that high mobility group box 1 (HMGB1), a chromosomal protein, plays a role in the regulation of the Hippo pathway during liver tumorigenesis. Cre/loxP recombination-mediated HMGB1 depletion in hepatocytes blocks diethylnitrosamine-induced liver cancer initiation in mice, whereas short hairpin RNA-mediated gene silencing of HMGB1 inhibits HCC cell proliferation. Mechanistically, the binding of HMGB1 to GA-binding protein alpha promotes the expression of yes-associated protein (YAP), a major downstream effector of the Hippo pathway that contributes to liver tumorigenesis by inducing hypoxia-inducible factor 1α (HIF1α)-dependent aerobic glycolysis. Like wild-type YAP-complementary DNA, YAP-5SA-S94A can restore HIF1α DNA binding activity, glycolysis-associated gene expression, and HIF1α-YAP complex formation in YAP-knockdown HCC cell lines. In contrast, verteporfin, a reagent targeting the interface between YAP and TEA domain transcription factor, has the ability to block YAP-HIF1α complex formation. Notably, genetic or pharmacologic inhibition of the HMGB1-YAP-HIF1α pathway confers protection against excessive glycolysis and tumor growth in mice.
conclusionThese findings demonstrate that HMGB1 plays a novel role in modulating the YAP-dependent HIF1α pathway and shed light on the development of metabolism-targeting therapeutics for HCC chemoprevention. (Hepatology 2018;67:1823-1841).
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