ArticleMolecular biology reports2021
Inhibitory effect of cathepsin K inhibitor (ODN-MK-0822) on invasion, migration and adhesion of human breast cancer cells in vitro.
Article in Molecular biology reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Cathepsin K Inhibitors as Potential Drugs for the Treatment of Osteoarthritis.International journal of molecular sciences · 2025Review
- The role of lysosomal peptidases in glioma immune escape: underlying mechanisms and therapeutic strategies.Frontiers in immunology · 2023Review
- Cathepsin K in Pathological Conditions and New Therapeutic and Diagnostic Perspectives.International journal of molecular sciences · 2022Review
- BAP1 phosphorylation-mediated Sp1 stabilization plays a critical role in cathepsin K inhibition-induced C-terminal p53-dependent Bax upregulation.Redox biology · 2022Article
- Overexpression of pressure-responsive miRNA-5703 inhibits pressure-induced growth and metastasis of liver cancer.Journal of Cancer · 2022Article
- Enhanced ZNF521 expression induces an aggressive phenotype in human ovarian carcinoma cell lines.PloS one · 2022Article
- Study on the Correlation between Pain and Cytokine Expression in the Peripheral Blood of Patients with Bone Metastasis of Malignant Cancer Treated Using External Radiation Therapy.Pain research & management · 2022Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Approximately 90% of patients with advanced breast cancer develop bone metastases; an event that results in severe decrease of quality of life and a drastic deterioration in prognosis. Therefore, to increase the survival of breast cancer patients, the development of new therapeutic strategies to impair metastatic process and skeletal complications is critical. Previous studies on the role of cathepsin K (CTSK) in metastatic spreading led to several strategies for inhibition of this molecule such as MIV-711 (Medivir), balicatib and odanacatib (ODN) which were on trial in the past. The present study intended to assess the anti-metastatic efficacy of ODN in breast cancer cells. Human breast cancer cell lines MDA-MB-231 were treated with different concentrations of ODN and performed invasion, adhesion and migration assays and, RT-PCR and western blot to evaluate the effect of ODN on the metastatic potential of breast cancer cells. ODN markedly decreased wound healing cell migration, invasion and adhesion at a dose dependent manner. ODN inhibits cell invasion by decreasing the matrix metalloproteinase (MMP-9) with the upregulation of TIMP-1 expression. ODN effectively inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal Kinase (JNK), and blocked the expression of β-integrins and FAK proteins. ODN also significantly inhibited PI3K downstream targets Rac1, Cdc42, paxillin and Src which are critical for cell adhesion, migration and cytoskeletal reorganization. ODN exerts anti-metastatic action through inhibition of signaling pathway for MMP-9, PI3K and MAPK. This indicates potential therapeutic effects of ODN in the treatment of metastatic breast cancer.
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