ArticleCells2022
Targeting PCSK9 in Liver Cancer Cells Triggers Metabolic Exhaustion and Cell Death by Ferroptosis.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 30 citations in OpenAlex.
- Role of PCSK9 in hallmarks of cancer: From mechanisms to interventions (Review).Oncology letters · 2026Review
- Targeting PCSK9 in Vascular Smooth Muscle Cells: An Effective Strategy to Suppress Ferroptosis and Attenuate Abdominal Aortic Aneurysm Progression.Cell proliferation · 2026Article
- Revisiting the Lipid-Cancer Axis: PCSK9, ANGPTL3, and CETP as Emerging Biomarkers and Therapeutic Targets in Oncology.Biomolecules · 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
- Regulatory mechanisms of hepatocyte PCSK9 expression: translating mechanistic insights into potential nutraceuticals.Chinese medicine · 2025Review
- Role of S-palmitoylation in digestive system diseases.Cell death discovery · 2025Review
- Prediction of the effect of Bupleurum chinensis DC. (Chaihu) on survival and its potential targets in hepatocellular carcinoma based on a prognostic model.BMC complementary medicine and therapies · 2025Article
- Mendelian Randomization Assessment of the Genetic Effects of Lipid-Lowering Drugs on Digestive System Cancers.Food science & nutrition · 2025Article
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- [Construction and Validation of A Prognostic Model for Lung Adenocarcinoma Based on Ferroptosis-related Genes].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Article
- Lipid metabolism abnormalities in pediatric abdominal solid malignant tumors: a comprehensive review.Frontiers in pediatrics · 2025Review
- A Novel Perspective on PCSK9 in Alzheimer's Disease: A Focus on Amyloid Beta.Current medicinal chemistry · 2025Review
- Nilotinib boosts the efficacy of anti-PDL1 therapy in colorectal cancer by restoring the expression of MHC-I.Journal of translational medicine · 2024Article
- Contrasting effects of intracellular and extracellular human PCSK9 on inflammation, lipid alteration and cell death.Communications biology · 2024Article
- The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer.World journal of gastrointestinal oncology · 2024Review
- Article
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Inhibition of PCSK9: A Promising Enhancer for Anti-PD-1/PD-L1 Immunotherapy.Research (Washington, D.C.) · 2024Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deregulated lipid metabolism is a common feature of liver cancers needed to sustain tumor cell growth and survival. We aim at taking advantage of this vulnerability and rewiring the oncogenic metabolic hub by targeting the key metabolic player pro-protein convertase subtilisin/kexin type 9 (PCSK9). We assessed the effect of PCSK9 inhibition using the three hepatoma cell lines Huh6, Huh7 and HepG2 and validated the results using the zebrafish in vivo model. PCSK9 deficiency led to strong inhibition of cell proliferation in all cell lines. At the lipid metabolic level, PCSK9 inhibition was translated by an increase in intracellular neutral lipids, phospholipids and polyunsaturated fatty acids as well as a higher accumulation of lipid hydroperoxide. Molecular signaling analysis involved the disruption of the sequestome 1/Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (p62/Keap1/Nrf2) antioxidative axis, leading to ferroptosis, for which morphological features were confirmed by electron and confocal microscopies. The anti-tumoral effects of PCSK9 deficiency were validated using xenograft experiments in zebrafish. The inhibition of PCSK9 was effective in disrupting the oncometabolic process, inducing metabolic exhaustion and enhancing the vulnerability of cancer cells to iron-triggered lipid peroxidation. We provide strong evidence supporting the drug repositioning of anti-PCSK9 approaches to treat liver cancers.
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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.