ArticleNature communications2018
Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 315 papers, 1 of them a synthesis that pooled it.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
315 citing papers in PubMed, 1 synthesis or guideline pooled it, 546 citations in OpenAlex.
- Metabolic reprogramming in hepatocellular carcinoma: a bibliometric and visualized study from 2011 to 2023.Frontiers in pharmacology · 2024Pooled it
- TRIM32-mediated ubiquitination of STING promotes glycolysis and tumor progression.Cell death and differentiation · 2026Article
- Spatial multi-omics guides ASCT2-targeted delivery of glycolysis inhibitor for cervical cancer suppression and chemoresistance reversal.Journal of advanced research · 2026Article
- HK2/VDAC1 Axis Regulates Malignant Progression of Esophageal Squamous Cell Carcinoma.Cancer medicine · 2026Article
- N-Acetylneuraminate Pyruvate Lyase Promotes Cell Adaptation to Glucose Deprivation by Regulating Intracellular ATP Levels.Current issues in molecular biology · 2026Article
- Deuterated polyunsaturated fatty acids alleviate in vitro skeletal muscle dysfunction induced by oxidative stress.Free radical biology & medicine · 2026Article
- Signal Transducer and Activator of Transcription (STAT) Proteins Regulate Mucosal-Associated Invariant T (MAIT) Cell Function.Immunology · 2026Article
- Research progress and therapeutic strategies in hepatocellular carcinoma metabolic reprogramming.Journal of advanced research · 2026Review
- Glucose metabolic reprogramming as a driver of immunosuppression in the tumour microenvironment.Clinical and translational medicine · 2026Review
- Lactylation and targeted therapy resistance in hepatocellular carcinoma.Clinical epigenetics · 2026Review
- H19 inhibition orchestrates DNMT3B-dependent epigenetic reprogramming of glycolytic enzymes in the liver during diabetes.Cell communication and signaling : CCS · 2026Article
- The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2026Review
- Ceramide-rich extracellular vesicles as pathogenic biomarkers in traumatic brain injury.bioRxiv : the preprint server for biology · 2026Article
- LYPLAL1 rare loss-of-function variants in humans and deletion in human hepatoma cells protect against MASLD.Journal of lipid research · 2026Article
- Src-mediated PHB2 phosphorylation disrupts mitochondrial cristae through cardiolipin dissociation in hepatocellular carcinoma.Redox biology · 2026Article
- ChIP-seq and RNA-seq Reveal the Involvement of Histone Lactylation Modification in Early Pregnancy with Subclinical Hypothyroidism.Biochemical genetics · 2026Article
- Article
- Crosstalk BetweenCancers · 2026Review
- A Unique Intercellular Feedforward Loop From HK1 to TGF-β1 Promotes the Progression of Hepatocellular Carcinoma.Journal of extracellular vesicles · 2026Article
- USP30-mediated Deubiquitination of Hexokinase 2 controls the metabolic fate of glucose and tumor progression.Cell death & disease · 2026Article
255 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) cells are metabolically distinct from normal hepatocytes by expressing the high-affinity hexokinase (HK2) and suppressing glucokinase (GCK). This is exploited to selectively target HCC. Hepatic HK2 deletion inhibits tumor incidence in a mouse model of hepatocarcinogenesis. Silencing HK2 in human HCC cells inhibits tumorigenesis and increases cell death, which cannot be restored by GCK or mitochondrial binding deficient HK2. Upon HK2 silencing, glucose flux to pyruvate and lactate is inhibited, but TCA fluxes are maintained. Serine uptake and glycine secretion are elevated suggesting increased requirement for one-carbon contribution. Consistently, vulnerability to serine depletion increases. The decrease in glycolysis is coupled to elevated oxidative phosphorylation, which is diminished by metformin, further increasing cell death and inhibiting tumor growth. Neither HK2 silencing nor metformin alone inhibits mTORC1, but their combination inhibits mTORC1 in an AMPK-independent and REDD1-dependent mechanism. Finally, HK2 silencing synergizes with sorafenib to inhibit tumor growth.
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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.