ArticleCancers2022
Rewiring Lipid Metabolism by Targeting PCSK9 and HMGCR to Treat Liver Cancer.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Role of PCSK9 in hallmarks of cancer: From mechanisms to interventions (Review).Oncology letters · 2026Review
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- Revisiting the Lipid-Cancer Axis: PCSK9, ANGPTL3, and CETP as Emerging Biomarkers and Therapeutic Targets in Oncology.Biomolecules · 2026Review
- Simvastatin in liver diseases: therapeutic value and research advances.Clinical and experimental medicine · 2026Review
- High levels of serum cholesterol increase the risk of developing vessel co-opting tumors in colorectal cancer liver metastases.The FEBS journal · 2026Article
- Revisiting cholesterol metabolism in hepatocellular carcinoma: a hidden driver of systemic therapy response.ESMO gastrointestinal oncology · 2026Review
- A survival prediction model for biliary tract cancer based on least absolute shrinkage and selection operator-cox regression.Annals of medicine · 2025Article
- ENO1-BACE2-mediated LDLR cleavage promotes liver cancer progression by remodelling cholesterol metabolism.Journal of molecular cell biology · 2025Article
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- [Strategies of statins for the prevention and treatment of hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- PCSK9 Manipulates Lipid Metabolism and the Immune Microenvironment in Cancer.OncoTargets and therapy · 2025Review
- The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Current Understanding of PCSK9 and Its Relevance to Cancer Prognosis and Immune Therapy: A Review.Iranian journal of pathology · 2024Review
- Dysregulated cholesterol regulatory genes in hepatocellular carcinoma.European journal of medical research · 2023Review
- Emergence of Lipid Droplets in the Mechanisms of Carcinogenesis and Therapeutic Responses.Cancers · 2023Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Alterations in lipid handling are an important hallmark in cancer. Our aim here is to target key metabolic enzymes to reshape the oncogenic lipid metabolism triggering irreversible cell breakdown. We targeted the key metabolic player proprotein convertase subtilisin/kexin type 9 (PCSK9) using a pharmacological inhibitor (R-IMPP) alone or in combination with 3-hydroxy 3-methylglutaryl-Coenzyme A reductase (HMGCR) inhibitor, simvastatin. We assessed the effect of these treatments using 3 hepatoma cell lines, Huh6, Huh7 and HepG2 and a tumor xenograft in chicken choriorallantoic membrane (CAM) model. PCSK9 deficiency led to dose-dependent inhibition of cell proliferation in all cell lines and a decrease in cell migration. Co-treatment with simvastatin presented synergetic anti-proliferative effects. At the metabolic level, mitochondrial respiration assays as well as the assessment of glucose and glutamine consumption showed higher metabolic adaptability and surge in the absence of PCSK9. Enhanced lipid uptake and biogenesis led to excessive accumulation of intracellular lipid droplets as revealed by electron microscopy and metabolic tracing. Using xenograft experiments in CAM model, we further demonstrated the effect of anti-PCSK9 treatment in reducing tumor aggressiveness. Targeting PCSK9 alone or in combination with statins deserves to be considered as a new therapeutic option in liver cancer clinical applications.
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What OpenQuestion holds
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.