ArticleJournal of hepatology2023
HILPDA promotes NASH-driven HCC development by restraining intracellular fatty acid flux in hypoxia.
Article in Journal of hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 46 citations in OpenAlex.
- Spatiotemporal dynamics of the host-tumor metabolic interface: Implications for precision nutritional oncology.Genes & diseases · 2026Review
- HILPDA, Regulated by WTAP in an m6A-Dependent Manner, Enhances Osteosarcoma Development by Inhibiting Ferroptosis and Promoting Glycolysis.Biochemical genetics · 2026Article
- Lipidomic Remodeling by HILPDA in Granulosa Cells Impairs Ovarian Reserve Through Disruption of Mitochondrial and Endoplasmic Reticulum Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Lipid droplet-associated gene signatures classify metabolic subtypes and identify PLIN3 as a key driver in hepatocellular carcinoma.Genes & diseases · 2026Article
- MYC promotes myocardial fibrosis via METTL1-mediated m7G modification of HILPDA.Biology direct · 2026Article
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- Lipid metabolism-related gene expression predicts prognostic outcomes in lung adenocarcinoma.Translational cancer research · 2026Article
- TRIM21-mediated degradation of HILPDA overcomes anti-PD-1 immunotherapy resistance in breast cancer by limiting PD-L1 palmitoylation.Oncogene · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Dietary glucuronolactone alleviates hepatic lipid accumulation via the enterohepatic axis in laying hens.Journal of animal science and biotechnology · 2026Article
- Blood metabolic panels for identifying significant fibrosis and inflammation in patients with MASLD.Cell reports. Medicine · 2026Article
- Organelle-specific regulation of ferroptosis.Biology direct · 2026Review
- Article
- Posaconazole mitigates α-amanitin-induced liver injury by inhibiting STT3B-mediated glycosylation and cellular uptake.Frontiers in pharmacology · 2026Article
- GPR34 inhibition reprograms tumor-associated macrophages and enhances the sensitivity of anti-PD-1 therapy in hepatocellular carcinoma.Cancer cell international · 2025Article
- Intranuclear paraspeckle-circular RNA TACC3 assembly forms RNA-DNA hybrids to facilitate MASH-related hepatocellular carcinoma growth in an mCancer communications (London, England) · 2025Article
- Lipid metabolism in cancer cells: Its role in hepatocellular carcinoma progression and therapeutic resistance.Hepatology communications · 2025Review
- Role of long-chain acyl-CoA synthetases in MASH-driven hepatocellular carcinoma and ferroptosis.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Molecular mechanisms in MASLD/MASH-related HCC.Hepatology (Baltimore, Md.) · 2025Review
- Role of lipid droplets in pulmonary arterial hypertension: focusing on pulmonary artery smooth muscle cell proliferation.Lipids in health and disease · 2025Review
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe prevalence of non-alcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) is rising rapidly, yet its underlying mechanisms remain unclear. Herein, we aim to determine the role of hypoxia-inducible lipid droplet associated protein (HILPDA)/hypoxia-inducible gene 2 (HIG2), a selective inhibitor of intracellular lipolysis, in NASH-driven HCC.
methodsThe clinical significance of HILPDA was assessed in human NASH-driven HCC specimens by immunohistochemistry and transcriptomics analyses. The oncogenic effect of HILPDA was assessed in human HCC cells and in 3D epithelial spheroids upon exposure to free fatty acids and either normoxia or hypoxia. Lipidomics profiling of wild-type and HILPDA knockout HCC cells was assessed via shotgun and targeted approaches. Wild-type (Hilpda
resultsIn patients with NASH-driven HCC, upregulated HILPDA expression is strongly associated with poor survival. In oxygen-deprived and lipid-loaded culture conditions, HILPDA promotes viability of human hepatoma cells and growth of 3D epithelial spheroids. Lack of HILPDA triggered flux of polyunsaturated fatty acids to membrane phospholipids and of saturated fatty acids to ceramide synthesis, exacerbating lipid peroxidation and apoptosis in hypoxia. The apoptosis induced by HILPDA deficiency was reversed by pharmacological inhibition of ceramide synthesis. In our experimental mouse model of NASH-driven HCC, Hilpda
conclusionsHepatic HILPDA is a pivotal oncometabolic factor in the NASH liver microenvironment and represents a potential novel therapeutic target. IMPACT AND IMPLICATIONS: Non-alcoholic steatohepatitis (NASH, chronic metabolic liver disease caused by buildup of fat, inflammation and damage in the liver) is emerging as the leading risk factor and the fastest growing cause of hepatocellular carcinoma (HCC), the most common form of liver cancer. While curative therapeutic options exist for HCC, it frequently presents at a late stage when such options are no longer effective and only systemic therapies are available. However, systemic therapies are still associated with poor efficacy and some side effects. In addition, no approved drugs are available for NASH. Therefore, understanding the underlying metabolic alterations occurring during NASH-driven HCC is key to identifying new cancer treatments that target the unique metabolic needs of cancer cells.
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