ArticleThe Journal of biological chemistry2011
Simvastatin prevents skeletal metastasis of breast cancer by an antagonistic interplay between p53 and CD44.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 143 citations in OpenAlex.
- Non-oncologic to oncologic drug: A systematic review of drug repurposing in cancer.Cancer chemotherapy and pharmacology · 2025Pooled it
- Statin use and breast cancer survival and risk: a systematic review and meta-analysis.Oncotarget · 2015Pooled it
- Trial
- Cholesterol-Lowering Treatment Blocks Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug Resistance in Breast and Colorectal Adenocarcinoma Models.Cancer medicine · 2026Article
- Statin use and risk of contralateral breast cancer: an updated cohort study with landmark analysis.European journal of epidemiology · 2026Article
- AΙ-Driven Drug Repurposing: Applications and Challenges.Medicines (Basel, Switzerland) · 2025Review
- Drug Repurposing in Veterinary Oncology: Myth or Reality?Veterinary sciences · 2025Review
- Statins and adhesion molecules: a review of a novel pleiotropic property of statins.Immunologic research · 2025Review
- Simvastatin inhibits proliferation and migration, promotes oxidative stress and ferroptosis in colon cancer.World journal of gastrointestinal oncology · 2025Article
- Statin use and risk of breast cancer among women with benign breast disease: a Danish nationwide cohort study.British journal of cancer · 2025Article
- Regulatory dynamics of Nanog in chondrocyte dedifferentiation: role of KLF4/p53 and p38/AKT signaling.Functional & integrative genomics · 2025Article
- Old drugs, new challenges: reassigning drugs for cancer therapies.Cellular & molecular biology letters · 2025Review
- Statins as Secondary Preventive Agent to Limit Breast Cancer Metastatic Outgrowth.International journal of molecular sciences · 2025Review
- Residual Traditional Risk in Non-Traditional Atherosclerotic Diseases.International journal of molecular sciences · 2025Review
- Drug repurposing for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Overcoming Resistance in Prostate Cancer Therapy Using a DZ-Simvastatin Conjugate.Molecular pharmaceutics · 2024Article
- Synergistic Effect of Layered Double Hydroxides Nanodosage Form to Induce Apoptosis and Ferroptosis in Breast Cancer.International journal of nanomedicine · 2024Article
- Tumoricidal Activity of Simvastatin in Synergy with RhoA Inactivation in Antimigration of Clear Cell Renal Cell Carcinoma Cells.International journal of molecular sciences · 2023Article
- Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer.BMC cancer · 2023Article
- Clinical verification of the relationship between serum lipid metabolism and immune activity in breast cancer patients treated with neoadjuvant chemotherapy.European journal of medical research · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Substantial data from clinical trials and epidemiological studies show promising results for use of statins in many cancers, including mammary carcinoma. Breast tumor primarily metastasizes to bone to form osteolytic lesions, causing severe pain and pathological fracture. Here, we report that simvastatin acts as an inhibitor of osteolysis in a mouse model of breast cancer skeletal metastasis of human mammary cancer cell MDA-MB-231, which expresses the mutant p53R280K. Simvastatin and lovastatin attenuated migration and invasion of MDA-MB-231 and BT-20 breast tumor cells in culture. Acquisition of phenotype to express the cancer stem cell marker, CD44, leads to invasive potential of the tumor cells. Interestingly, statins significantly decreased the expression of CD44 protein via a transcriptional mechanism. shRNA-mediated down-regulation of CD44 markedly reduced the migration and invasion of breast cancer cells in culture. We identified that in the MDA-MB-231 cells, simvastatin elevated the levels of mutated p53R280K, which was remarkably active as a transcription factor. shRNA-derived inhibition of mutant p53R280K augmented the expression of CD44, leading to increased migration and invasion. Finally, we demonstrate an inverse correlation between expression of p53 and CD44 in the tumors of mice that received simvastatin. Our results reveal a unique function of statins, which foster enhanced expression of mutant p53R280K to prevent breast cancer cell metastasis to bone.
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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 OpenQuestion graph.