ArticleClinical & experimental metastasis2002
Lovastatin alters cytoskeleton organization and inhibits experimental metastasis of mammary carcinoma cells.
Article in Clinical & experimental metastasis, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 66 citations in OpenAlex.
- Do Statins Affect Thyroid Volume and Nodule Size in Patients with Hyperlipidemia in a Region with Mild-to-Moderate Iodine Deficiency? A Prospective Study.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2018Trial
- The effect of concomitant drugs on oncological outcomes in patients treated with immunotherapy for metastatic urothelial carcinoma: a narrative review.Oncology research · 2025Review
- An ivermectin - atorvastatin combination impairs nuclear transport inhibiting dengue infectioniScience · 2023Article
- The Involvement of Hypoxia in the Response of Neuroblastoma Cells to the Exposure of Atorvastatin.Current issues in molecular biology · 2023Article
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- Natural Compounds as Target Biomolecules in Cellular Adhesion and Migration: From Biomolecular Stimulation to Label-Free Discovery and Bioactivity-Based Isolation.Biomedicines · 2021Review
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- Pleiotropic effects of statins: A focus on cancer.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Repurposing of host-based therapeutic agents for the treatment of coronavirus disease 2019 (COVID-19): a link between antiviral and anticancer mechanisms?International journal of antimicrobial agents · 2020Article
- New drugs are not enough‑drug repositioning in oncology: An update.International journal of oncology · 2020Review
- Inhibiting Airway Smooth Muscle Contraction Using Pitavastatin: A Role for the Mevalonate Pathway in Regulating Cytoskeletal Proteins.Frontiers in pharmacology · 2020Article
- Statin drugs to reduce breast cancer recurrence and mortality.Breast cancer research : BCR · 2018Review
- Rho GTPases as therapeutic targets in cancer (Review).International journal of oncology · 2017Review
- Addition of vasopressin synthetic analogue [V(4)Q(5)]dDAVP to standard chemotherapy enhances tumour growth inhibition and impairs metastatic spread in aggressive breast tumour models.Clinical & experimental metastasis · 2016Article
- Integrin β3 and LKB1 are independently involved in the inhibition of proliferation by lovastatin in human intrahepatic cholangiocarcinoma.Oncotarget · 2016Article
- Statins and breast cancer stage and mortality in the Women's Health Initiative.Cancer causes & control : CCC · 2015Article
- Targeting the mevalonate cascade as a new therapeutic approach in heart disease, cancer and pulmonary disease.Pharmacology & therapeutics · 2014Review
- Expression of PTRF in PC-3 Cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways.Molecular & cellular proteomics : MCP · 2012Article
- Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states.Molecular and cellular endocrinology · 2010Review
- Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway.Journal of experimental & clinical cancer research : CR · 2010Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lovastatin is a competitive inhibitor of 3-hydroxy 3-methylglutaryl coenzyme A reductase, the key regulatory enzyme of cholesterol biosynthesis. This enzyme catalyzes the formation of mevalonate, which is also the precursor of isoprenoid moieties, such as farnesol and geraniol, that are incorporated into several molecules essential for tumor cell signaling. Here, we describe that pretreatment with a non-cytotoxic concentration of lovastatin (10 microM) dramatically inhibited the metastatic ability of F311 mammary carcinoma cells in syngeneic BALB/c mice. Similarly, daily i.p. treatment of animals with a well-tolerated dose of lovastatin (10 mg/kg/day) significantly reduced the number of experimental lung metastases. In vitro, incubation of F3II monolayers in the presence of lovastatin caused a rounded-cell morphology. Immunofluorescence analysis revealed a lack of cortical actin organization, micrutubule disruption and inhibition of integrin-mediated focal contacts in lovastatin-treated cells. Exposure of F3II cells to lovastatin significantly inhibited tumor cell adhesion and migration, and coincubation with the cholesterol precursor mevalonate prevented these effects. Lovastatin reduced membrane localization of Rho protein, a signaling molecule involved in the regulation of actin-based cell motility that needs geranylation for membrane association and activation. In addition, lovastatin induced a dose-dependent inhibition in the secretion of urokinase, a key proteolytic enzyme during tumor invasion and metastasis, and a significant increase of tissue-type plasminogen activator, a marker of good prognosis in mammary cancer. These data suggest that antimetastatic properties of lovastatin are strongly associated with alterations in cytoskeleton organization and the consequent modulation of adhesion, motility and proteolysis.
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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.