ArticleThe Journal of biological chemistry2008
Blockade of the RhoA-JNK-c-Jun-MMP2 cascade by atorvastatin reduces osteosarcoma cell invasion.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
60 citing papers in PubMed, 137 citations in OpenAlex.
- Regulation of Blood-Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer's Disease and Brain Tumors.Molecules (Basel, Switzerland) · 2025Review
- Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targets.Journal of bone oncology · 2025Review
- C-terminal binding protein-2 triggers CYR61-induced metastatic dissemination of osteosarcoma in a non-hypoxic microenvironment.Journal of experimental & clinical cancer research : CR · 2025Article
- FSP1-mediated ferroptosis in cancer: from mechanisms to therapeutic applications.Apoptosis : an international journal on programmed cell death · 2024Review
- Metabolic reprogramming in osteosarcoma.Pediatric discovery · 2023Review
- Comparison of Selected Non-Coding RNAs and Gene Expression Profiles between Common Osteosarcoma Cell Lines.Cancers · 2022Article
- [Atorvastatin inhibits malignant behaviors and induces apoptosis in human glioma cells by up-regulating miR-146a and inhibiting the PI3K/Akt signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Article
- Atorvastatin regulates the migration and invasion of prostate cancer through the epithelial-mesenchymal transformation and matrix metalloproteinase pathways.Investigative and clinical urology · 2022Article
- Synergistic Anti-Tumor Effect of Simvastatin Combined to Chemotherapy in Osteosarcoma.Cancers · 2021Article
- TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway.International journal of oncology · 2021Article
- lncRNA SNHG1 Promotes Basal Bladder Cancer Invasion via Interaction with PP2A Catalytic Subunit and Induction of Autophagy.Molecular therapy. Nucleic acids · 2020Article
- Dehydrocorydaline inhibits the tumorigenesis of breast cancer MDA‑MB‑231 cells.Molecular medicine reports · 2020Article
- Wnt/β‑catenin signaling modulates piperine‑mediated antitumor effects on human osteosarcoma cells.Molecular medicine reports · 2020Article
- Article
- The tetraspanin CD81 mediates the growth and metastases of human osteosarcoma.Cellular oncology (Dordrecht, Netherlands) · 2019Article
- CYR61 triggers osteosarcoma metastatic spreading via an IGF1Rβ-dependent EMT-like process.BMC cancer · 2019Article
- Somatostatin Maintains Permeability and Integrity of Blood-Brain Barrier in β-Amyloid Induced Toxicity.Molecular neurobiology · 2019Article
- Astragalus polysaccharides decrease proliferation, migration, and invasion but increase apoptosis of human osteosarcoma cells by up-regulation of microRNA-133a.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2018Article
- The Anti-Angiogenic Effect of Atorvastatin in Glioblastoma Spheroids Tumor Cultured in Fibrin Gel: in 3D in Vitro ModelAsian Pacific journal of cancer prevention : APJCP · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma is characterized by a high malignant and metastatic potential, which points to the need for new therapeutic strategies to prevent cell metastasis. In this study, we show that statin-induced HMG-CoA reductase inhibition reduces cell migration and invasion in human and murine osteosarcoma cells, independently of the genotype. The statin-induced reduction of cell migration and invasion was independent of induction of apoptosis and was geranylgeranylpyrophosphate-dependent. The statin reduced matrix metalloproteinase (MMP) 2, 9, and 14 and TIMP2 expression or activity in invading cells. Forced expression of MMP2 and MMP14 overcame the inhibitory effect of the statin on cell invasion, suggesting a role for these MMPs in invasive potential. We also investigated the mechanisms involved in the reduced MMP2 activity and cell invasion. Inhibition of JNK, but not ERK1/2 signaling, reduced MMP2 activity. Pharmacological or constitutive activation of JNK overcame the reduced MMP2 activity and cell invasion induced by the statin. The statin decreased JNK phosphorylation and c-Jun nuclear translocation, suggesting that HMG-CoA reductase inhibition targets the JNK-c-Jun signaling pathway. We showed that mevalonate or geranylgeranylpyrophosphate treatment prevented the statin-induced reduction in JNK phosphorylation, MMP2 activity, and cell invasion. Forced expression of a constitutively active form of RhoA increased JNK phosphorylation and overcame the inhibitory effect of atorvastatin on MMP2 activity and cell invasion. The data establish a link between RhoA, JNK, c-Jun, and MMP2 activity that is functionally involved in the reduction in osteosarcoma cell invasion by the statin. This suggests a novel strategy targeting RhoA-JNK-c-Jun signaling to reduce osteosarcoma cell tumorigenesis.
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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.