ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
PCSK9 Promotes the Malignancy of Triple-negative Breast Cancer Cells by Reducing Cholesterol Levels at the Plasma Membrane to Activate EGFR and HER3.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
7 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
- Article
- Revisiting the Lipid-Cancer Axis: PCSK9, ANGPTL3, and CETP as Emerging Biomarkers and Therapeutic Targets in Oncology.Biomolecules · 2026Review
- Roles of Her3 in carcinogenesis and advances in Her3-targeted cancer therapy.Discover oncology · 2026Review
- Dynamic Metabolic States in TNBC: Orchestrating Spatiotemporal Adaptation and Therapy.Oncology research · 2026Review
- PCSK9 in Cancer: Biological Mechanisms and Implications for Therapeutic Resistance.Biomolecules · 2025Review
- PCSK9 Promotes the Malignancy of Triple-negative Breast Cancer Cells by Reducing Cholesterol Levels at the Plasma Membrane to Activate EGFR and HER3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Triple-negative breast cancer (TNBC) is a highly heterogeneous and clinically aggressive disease with the highest mortality rate among all subtypes of breast cancer. To discover new driver genes for metastatic TNBC, this work compares the transcription profiles of MDA-MB-231-GFP cells and 231-GFP-derived lung metastatic cells (4-11). Results reveal that proprotein convertase subtilisin/kexin type 9 (PCSK9) is highly upregulated in 4-11 cells. Knockdown of PCSK9 greatly decreases the tumorigenic and metastatic potential of 4-11 cells, whereas overexpression of PCSK9 significantly enhances tumor maliganancy. Mechanistically, the binding of PCSK9 to the low-density lipoprotein receptor (LDLR) results in decreased LDLR at the plasma membrane, which further decreases cholesterol and lipid raft in the plasma membrane and activates human epidermal growth factor receptor 1 and 3 (EGFR and HER3). Subsequently, phosphorylated EGFR and HER3 activate the Src/ERK/c-Jun to increase the levels of cyclin D3 and vimentin and thereby enhance cell growth and metastasis. Metadata analyses also reveal that TNBC patients with high PCSK9 expression exhibited worse clinical outcomes. Taken together, these findings not only reveal a novel mechanism by which PCSK9 promotes the malignant potential of TNBC but also indicate that PCSK9 is a potential therapeutic target for treating TNBC patients.
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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 Socratic graph.