ArticleCell communication and signaling : CCS2019
Cholesterol content in cell membrane maintains surface levels of ErbB2 and confers a therapeutic vulnerability in ErbB2-positive breast cancer.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 3 of them syntheses that pooled it.
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72 citing papers in PubMed, 3 syntheses or guidelines pooled it, 127 citations in OpenAlex.
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- The prognostic significance of controlling nutritional status (CONUT) score for surgically treated renal cell cancer and upper urinary tract urothelial cancer: a systematic review and meta-analysis.European journal of clinical nutrition · 2022Pooled it
- Cholesterol and Its Derivatives: Multifaceted Players in Breast Cancer Progression.Frontiers in oncology · 2022Pooled it
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- Cholesterol-Lowering Treatment Blocks Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug Resistance in Breast and Colorectal Adenocarcinoma Models.Cancer medicine · 2026Article
- The Many Layers of Membrane Biophysics: Environment-Sensitive Fluorophores Report on Structural Organization of Biological Membranes at Various Depths.Analytical chemistry · 2026Article
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- Computational Elucidation of Sterol Recognition by SREBP Cleavage Activatory Protein.Journal of chemical information and modeling · 2025Article
- Cholesterol-dependent dimerization and conformational dynamics of EphA2 receptors from coarse-grained and all-atom simulations.Structure (London, England : 1993) · 2025Article
- Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen Species.Cells · 2025Article
- Raman analysis of lipids in cells: Current applications and future prospects.Journal of pharmaceutical analysis · 2025Review
- Impact of Shenling Baizhu Powder on lipid profiles and body mass index in breast cancer patients under adjuvant chemotherapy: a retrospective study.Translational cancer research · 2025Article
- Xanthohumol Sensitizes Melanoma Cells to Vemurafenib by Lowering Membrane Cholesterol and Increasing Membrane Fluidity.International journal of molecular sciences · 2025Article
- Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment.Molecular cancer · 2025Review
- Cholesterol suppresses AMFR-mediated PDL1 ubiquitination and degradation in HCC.Molecular and cellular biochemistry · 2025Article
12 more citing papers are in PubMed but not listed here.
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17 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundErbB2 overexpression identifies a subset of breast cancer as ErbB2-positive and is frequently associated with poor clinical outcomes. As a membrane-embedded receptor tyrosine kinase, cell surface levels of ErbB2 are regulated dynamically by membrane physical properties. The present study aims to investigate the influence of membrane cholesterol contents on ErbB2 status and cellular responses to its tyrosine kinase inhibitors.
methodsThe cholesterol abundance was examined in ErbB2-positive breast cancer cells using filipin staining. Cellular ErbB2 localizations were investigated by immunofluorescence with altered membrane cholesterol contents. The inhibitory effects of the cholesterol-lowering drug lovastatin were assessed using cell proliferation, apoptosis, immunoblotting and immunofluorescence assays. The synergistic effects of lovastatin with the ErbB2 inhibitor lapatinib were evaluated using an ErbB2-positive breast cancer xenograft mouse model.
resultsMembrane cholesterol contents positively correlated with cell surface distribution of ErbB2 through increasing the rigidity and decreasing the fluidity of cell membranes. Reduction in cholesterol abundance assisted the internalization and degradation of ErbB2. The cholesterol-lowering drug lovastatin significantly potentiated the inhibitory effects of ErbB2 kinase inhibitors, accompanied with enhanced ErbB2 endocytosis. Lovastatin also synergized with lapatinib to strongly suppress the in vivo growth of ErbB2-positive breast cancer xenografts.
conclusionThe cell surface distribution of ErbB2 was closely regulated by membrane physical properties governed by cholesterol contents. The cholesterol-lowering medications can hence be exploited for potential combinatorial therapies with ErbB2 kinase inhibitors in the clinical treatment of ErbB2-positive breast cancer.
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