ArticleProceedings of the National Academy of Sciences of the United States of America2011
Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 196 papers.
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Who cites it
196 citing papers in PubMed, 401 citations in OpenAlex.
- Tissue-specific molecular responses to salinomycin and their modulation by ionophore-antibiotic interactions in turkeys.Poultry science · 2026Article
- Targeting the WNT/β-Catenin Pathway in Hematological Malignancies: From Molecular Pathogenesis to Emerging Therapeutic Strategies.Biomolecules · 2026Review
- MHC disparity hampers thymus-dependent T-cell recovery post-hematopoietic transplantation through dysregulation of TGF-β1 and LRP6 pathways.Haematologica · 2026Article
- PFDN2 stabilizes PYCR2 to activate Wnt/β-catenin signaling and promote colorectal cancer progression.Scientific reports · 2026Article
- The structure and functions of TRAF families and recent advances of TRAFs in leukemia.Frontiers in oncology · 2026Review
- Therapeutic Potential of Ion Carrier Antibiotics in Ovarian Cancer: Mechanisms and Prospects.Cancer management and research · 2026Review
- Combined drugs-loaded nano-lipodisk carrier for pH-responsive delivery for improved therapeutic potential on lung cancer model.Journal of biological engineering · 2025Article
- Cloning and Expression ofAnimals : an open access journal from MDPI · 2025Article
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- Small-sized twin-nanoparticles normalize tumor vasculature to enhance tumor accumulation and penetration for potent eradication of cancer stem-like cells.Acta pharmaceutica Sinica. B · 2025Article
- Nanotherapeutic strategies exploiting biological traits of cancer stem cells.Bioactive materials · 2025Review
- Wnt/β-Catenin Signaling Regulates Hepatitis B Virus cccDNA Levels.International journal of molecular sciences · 2025Article
- Regulatory effect of Wnt signaling on mitochondria in cancer: from mechanism to therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Low-Dose Salinomycin Alters Mitochondrial Function and Reprograms Global Metabolism in Burkitt Lymphoma.International journal of molecular sciences · 2025Article
- Article
- Polyphenol-Based Prevention and Treatment of Cancer Through Epigenetic and Combinatorial Mechanisms.Nutrients · 2025Review
- Pan-cancer drivers of metastasis.Molecular cancer · 2025Article
- Wnt Signaling Pathway in Tumor Biology.Genes · 2024Review
- Increased Trypanocidal Activity of the Salinomycin Derivative Ironomycin Is Due to ROS Production and Iron Uptake Impairment.Molecules (Basel, Switzerland) · 2024Article
- Blocking the WNT/β-catenin pathway in cancer treatment:pharmacological targets and drug therapeutic potential.Heliyon · 2024Review
136 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Salinomycin, an antibiotic potassium ionophore, has been reported recently to act as a selective breast cancer stem cell inhibitor, but the biochemical basis for its anticancer effects is not clear. The Wnt/β-catenin signal transduction pathway plays a central role in stem cell development, and its aberrant activation can cause cancer. In this study, we identified salinomycin as a potent inhibitor of the Wnt signaling cascade. In Wnt-transfected HEK293 cells, salinomycin blocked the phosphorylation of the Wnt coreceptor lipoprotein receptor related protein 6 (LRP6) and induced its degradation. Nigericin, another potassium ionophore with activity against cancer stem cells, exerted similar effects. In otherwise unmanipulated chronic lymphocytic leukemia cells with constitutive Wnt activation nanomolar concentrations of salinomycin down-regulated the expression of Wnt target genes such as LEF1, cyclin D1, and fibronectin, depressed LRP6 levels, and limited cell survival. Normal human peripheral blood lymphocytes resisted salinomycin toxicity. These results indicate that ionic changes induced by salinomycin and related drugs inhibit proximal Wnt signaling by interfering with LPR6 phosphorylation, and thus impair the survival of cells that depend on Wnt signaling at the plasma membrane.
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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.