ArticleNature metabolism2022
HK1 from hepatic stellate cell-derived extracellular vesicles promotes progression of hepatocellular carcinoma.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 113 citations in OpenAlex.
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- Activated hepatic stellate cell-derived exosomal miR-23a-3p promotes hepatocellular carcinogenesis by regulating DUSP5/ERK signaling.Journal of advanced research · 2026Article
- Targeting LDHA Palmitoylation Sensitizes GBM to Chemoradiotherapy via Suppressing Palmitic Acid Induced Glycolytic Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emerging roles of α/β hydrolase domain (ABHD) proteins in S-palmitoylation modification: molecular mechanisms, structural features, and pathological implications.Cellular & molecular biology letters · 2026Review
- Palmitoylation-related gene signature for immune subtyping, prognostic stratification, and immunotherapy guidance in hepatocellular carcinoma.Translational cancer research · 2026Article
- O-GlcNAcylation: the metabolic-immune translator in tumor evolution and treatment.Molecular medicine (Cambridge, Mass.) · 2026Review
- IRF7 links HK1-dependent histone lactylation to fibroblast activation and cardiac fibrosis.EMBO molecular medicine · 2026Article
- Hexokinase-3 upregulation and histone H3K18 lactylation mediate murine liver fibrosis induced by Echinococcus multilocularis.PLoS neglected tropical diseases · 2026Article
- The metabolic plasticity of cancer stem cells: bidirectional crosstalk with organ-resident cells.Experimental & molecular medicine · 2026Review
- Cargo-driven extracellular vesicles as pharmaceutical nanocarriers: A pharmaceutics-oriented comparison of animal exosomes and plant-derived exosome-like nanoparticles.International journal of pharmaceutics: X · 2026Review
- Toxoplasma GRA72 is Involved in Membrane-Associated Functions and Metabolic Homeostasis Revealed by Transcriptomic Analysis.Acta parasitologica · 2026Article
- Developing blood extracellular vesicle protein biomarkers for hepatocellular carcinoma: mechanisms, methods, and translation.Journal of nanobiotechnology · 2026Review
- Visualizing extracellular vesicles in cancer: from biogenesis to theranostic applications.Journal of nanobiotechnology · 2026Review
- <p>KMO downregulation promotes hepatocellular carcinoma growth via 3‑HAA‑mediated mitochondrial mass and function imbalances</p>.International journal of oncology · 2026Article
- A Unique Intercellular Feedforward Loop From HK1 to TGF-β1 Promotes the Progression of Hepatocellular Carcinoma.Journal of extracellular vesicles · 2026Article
- HBV reprograms the tumor microenvironment in hepatocellular carcinoma: mechanisms and therapeutic implications.Clinical and experimental medicine · 2026Review
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- A Cori cycle-related gene signature predicts prognosis, immune microenvironment, and drug response in breast cancer.Translational cancer research · 2026Article
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- PFKFB3 Mediated Glycolytic Reprogramming Drives Vascular Endothelial Injury Under Chronic Intermittent Hypoxia.International journal of biological sciences · 2026Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular vesicles play crucial roles in intercellular communication in the tumor microenvironment. Here we demonstrate that in hepatic fibrosis, TGF-β stimulates the palmitoylation of hexokinase 1 (HK1) in hepatic stellate cells (HSCs), which facilitates the secretion of HK1 via large extracellular vesicles in a TSG101-dependent manner. The large extracellular vesicle HK1 is hijacked by hepatocellular carcinoma (HCC) cells, leading to accelerated glycolysis and HCC progression. In HSCs, the nuclear receptor Nur77 transcriptionally activates the expression of depalmitoylase ABHD17B to inhibit HK1 palmitoylation, consequently attenuating HK1 release. However, TGF-β-activated Akt functionally represses Nur77 by inducing Nur77 phosphorylation and degradation. We identify the small molecule PDNPA that binds Nur77 to generate steric hindrance to block Akt targeting, thereby disrupting Akt-mediated Nur77 degradation and preserving Nur77 inhibition of HK1 release. Together, this study demonstrates an overlooked function of HK1 in HCC upon its release from HSCs and highlights PDNPA as a candidate compound for inhibiting HCC progression.
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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.