ArticleCell2025
A commonly inherited human PCSK9 germline variant drives breast cancer metastasis via LRP1 receptor.
Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07061535 (Efficacy and Safety of Sintilimab Combined With Tafolecimab and Chemotherapy as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer), which is not on this map. Cited by 26 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.
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.
Efficacy and Safety of Sintilimab Combined With Tafolecimab and Chemotherapy as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer (STAR-SCLC)：A Prospective, Single Arm Trial
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Role of PCSK9 in breast cancer: a systematic review of its mechanistic pathways and clinical relevance.Frontiers in pharmacology · 2026Pooled it
- Hereditary breast cancer: emerging roles of non-coding RNAs.Hereditas · 2026Review
- Role of PCSK9 in hallmarks of cancer: From mechanisms to interventions (Review).Oncology letters · 2026Review
- Tumor-derived PCSK9-enriched exosomes reprogram adipocytes to drive metabolic dysregulation and immune evasion in triple-negative breast cancer.Cell death & disease · 2026Article
- PCSK9 and Breast Cancer Survival: A Mendelian Randomization Study.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Self-fueling catalysis-driven membrane destabilization triggers CSC-enriched tumors ablation.Journal of nanobiotechnology · 2026Article
- Loss of Mast cells and histaminergic signaling link diet to platelet-mediated NETosis and mammary cancer recurrence.bioRxiv : the preprint server for biology · 2026Article
- PCSK9-mediated degradation of cell-surface LDL receptors impairs human CD8+ T cell effector functions.iScience · 2026Article
- Margin of Error: The Emerging Role of Field Cancerization in Predicting Recurrence Risk of Ductal Carcinoma In Situ.International journal of molecular sciences · 2026Review
- PCSK5M452I Is a Recessive Hypomorph Exclusive to MCF10DCIS.com Cells.Molecular cancer research : MCR · 2026Article
- PCSK9 expression and cancer survival: a prognostic biomarker at the intersection of oncology and geroscience.GeroScience · 2026Article
- High resolution genome-wide SNP array analyses on matched colorectal-based lung and brain metastases.Journal of cancer research and clinical oncology · 2026Article
- Article
- Review
- piR-43452 suppresses bladder cancer progression and enhances gemcitabine sensitivity via GTSF1/PIWIL4-mediated LRP1 mRNA destabilization.Translational oncology · 2026Article
- Targeted therapy in patients with genetic tumor syndromes.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Photothermal Combination Therapy for Metastatic Breast Cancer: A New Strategy and Future Perspectives.Biomedicines · 2025Review
- Cardiovascular Disease Meets Cancer: Exploring the Epidemiology in China and Homotherapy Targeting Intersectional Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- The Impact of PCSK9 on Diabetic Cardiomyopathy: Mechanisms and Implications.Biomolecules · 2025Review
- Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Identifying patients at risk for metastatic relapse is a critical medical need. We identified a common missense germline variant in proprotein convertase subtilisin/kexin type 9 (PCSK9) (rs562556, V474I) that is associated with reduced survival in multiple breast cancer patient cohorts. Genetic modeling of this gain-of-function single-nucleotide variant in mice revealed that it causally promotes breast cancer metastasis. Conversely, host PCSK9 deletion reduced metastatic colonization in multiple breast cancer models. Host PCSK9 promoted metastatic initiation events in lung and enhanced metastatic proliferative competence by targeting tumoral low-density lipoprotein receptor related protein 1 (LRP1) receptors, which repressed metastasis-promoting genes XAF1 and USP18. Antibody-mediated therapeutic inhibition of PCSK9 suppressed breast cancer metastasis in multiple models. In a large Swedish early-stage breast cancer cohort, rs562556 homozygotes had a 22% risk of distant metastatic relapse at 15 years, whereas non-homozygotes had a 2% risk. Our findings reveal that a commonly inherited genetic alteration governs breast cancer metastasis and predicts survival-uncovering a hereditary basis underlying breast cancer metastasis.
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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.