ArticleFrontiers in pharmacology2020
Simvastatin Suppresses Human Breast Cancer Cell Invasion by Decreasing the Expression of Pituitary Tumor-Transforming Gene 1.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.
- Impact of statin use on breast cancer recurrence and mortality before and after diagnosis: a systematic review and meta-analysis.Frontiers in oncology · 2023Pooled it
- Statins as Repurposed Drugs in Gynecological Cancer: A Review.International journal of molecular sciences · 2022Pooled it
- Recent Progress in Exosome-Derived Nanocarriers for Breast Cancer Therapy: Advances, Translational Barriers, and Scale-Up Considerations.Pharmaceutical research · 2026Review
- Statin use and risk of contralateral breast cancer: an updated cohort study with landmark analysis.European journal of epidemiology · 2026Article
- PTTG1-mediated the transcription of c-myc promotes retinoblastoma progression.Cell division · 2026Article
- Pharmacological combination of simvastatin and doxorubicin reduces tumor growth and lung metastasis in triple-negative breast cancer.Frontiers in cell and developmental biology · 2026Article
- Inhibition of PTTG1 suppresses proliferation and promotes differentiation of neuroblastoma cells by inducing autophagy.Pediatric surgery international · 2025Article
- Simvastatin inhibits the immunosuppressive effects of endometrial cancer-associated mesenchymal stem cells through TGF-β2/SMAD2/3 signaling and reduces tumor growth.Scientific reports · 2025Article
- Statin use and risk of breast cancer among women with benign breast disease: a Danish nationwide cohort study.British journal of cancer · 2025Article
- The Role of RAC2 and PTTG1 in Cancer Biology.Cells · 2025Review
- Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics.Pharmaceutical research · 2025Review
- Targeting the Molecules in EMT: A Potential Therapeutic Opportunity in Breast Cancer.Current molecular medicine · 2025Review
- Emerging Roles of PTTG1/Securin in Breast Cancer.Journal of Cancer · 2025Review
- Exploring Prognostic Gene Factors in Breast Cancer via Machine Learning.Biochemical genetics · 2024Article
- DeepFGRN: inference of gene regulatory network with regulation type based on directed graph embedding.Briefings in bioinformatics · 2024Article
- "Pulsed Hypoxia" Gradually Reprograms Breast Cancer Fibroblasts into Pro-Tumorigenic Cells via Mesenchymal-Epithelial Transition.International journal of molecular sciences · 2023Article
- Statins for Cardiac and Vascular Protection During and After Cancer Therapy.Current oncology reports · 2022Review
- Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions.Acta pharmaceutica Sinica. B · 2022Review
- New Advances in Targeted Therapy of HER2-Negative Breast Cancer.Frontiers in oncology · 2022Review
- Simvastatin in the Treatment of Colorectal Cancer: A Review.Evidence-based complementary and alternative medicine : eCAM · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, have been widely used to lower cholesterol and prevent cardiovascular diseases. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer, while the underlying mechanisms remain to be elucidated. Herein, we sought to investigate the effect of statins on the expression of pituitary tumor-transforming gene 1 (PTTG1), a critical gene involved in human breast cancer invasion and metastasis. Our results showed that PTTG1 is highly expressed in malignant Hs578T and MDA-MB-231 breast cancer cell lines as compared with normal or less malignant breast cancer cells. Furthermore, we found that the expression of PTTG1 was markedly suppressed by lipophilic statins, such as simvastatin, fluvastatin, mevastatin, and lovastatin, but not by hydrophilic pravastatin. In a dose and time dependent manner, simvastatin suppressed PTTG1 expression by decreasing PTTG1 mRNA stability in MDA-MB-231 cells. Both siRNA-mediated knockdown of PTTG1 expression and simvastatin treatment markedly inhibited MDA-MB-231 cell invasion, MMP-2 and MMP-9 activity, and the expression of PTTG1 downstream target genes, while ectopic expression of PTTG1 promoted cancer cell invasion, and partly reversed simvastatin-mediated inhibition of cell invasion. Mechanistically, we found that inhibition of PTTG1 expression by simvastatin was reversed by geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate, suggesting the involvement of geranylgeranyl synthesis in regulating PTTG1 expression. Our results identified statins as novel inhibitors of PTTG1 expression in breast cancer cells and provide mechanistic insights into how simvastatin prevent breast cancer metastasis as observed in recent preclinical and clinical studies.
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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.