ArticleNeoplasia (New York, N.Y.)2010
Small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling induces apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo.
Article in Neoplasia (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 114 citations in OpenAlex.
- Targeting the WNT/β-Catenin Pathway in Hematological Malignancies: From Molecular Pathogenesis to Emerging Therapeutic Strategies.Biomolecules · 2026Review
- CK1α agonists attenuate medulloblastoma stemness and relapse risk.Cell death & disease · 2026Article
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- Wnt signaling and tumors (Review).Molecular and clinical oncology · 2024Review
- Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy.Journal of hematology & oncology · 2024Review
- Immunohistochemical Investigation into Protein Expression Patterns of FOXO4, IRF8 and LEF1 in Canine Osteosarcoma.Cancers · 2024Article
- Article
- Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study.Annals of the rheumatic diseases · 2022Article
- Targeting β-catenin in acute myeloid leukaemia: past, present, and future perspectives.Bioscience reports · 2022Review
- β-Catenin signaling in hepatocellular carcinoma.The Journal of clinical investigation · 2022Review
- Differential Levels of mRNAs in Normal B Lymphocytes, Monoclonal B Lymphocytosis and Chronic Lymphocytic Leukemia Cells from the Same Family Identify Susceptibility Genes.Oncology and therapy · 2021Article
- G3BP1 promotes human breast cancer cell proliferation through coordinating with GSK-3β and stabilizing β-catenin.Acta pharmacologica Sinica · 2021Article
- Wnt/β-catenin signaling in cancers and targeted therapies.Signal transduction and targeted therapy · 2021Review
- IGHG1 upregulation promoted gastric cancer malignancy via AKT/GSK-3β/β-Catenin pathway.Cancer cell international · 2021Article
- Adrenal cortex renewal in health and disease.Nature reviews. Endocrinology · 2021Review
- Quercetin shortened survival of radio-resistant B-1 cellsOncotarget · 2021Article
- HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia.Journal of translational medicine · 2021Article
- Deciphering the role of Wnt signaling in acute myeloid leukemia prognosis: how alterations in DNA methylation come into play in patients' prognosis.Journal of cancer research and clinical oncology · 2020Review
- Article
- Differences in expression and function of LEF1 isoforms in normal versus leukemic hematopoiesis.Leukemia · 2020Article
12 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
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLymphoid enhancer factor-1 (lef-1) is overexpressed in B-cell chronic lymphocytic leukemia (CLL) when compared with normal B cells and transcribes several genes implicated in the pathogenesis of CLL. We therefore hypothesize that antagonism of lef-1 might lead to killing of CLL cells. We used two small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling (CGP049090 and PKF115-584) to test our hypothesis. DESIGN AND
methodsEnriched CLL cells and healthy B cells were used in this study. Small interfering RNA (siRNA)-mediated knockdown of lef-1 in primary CLL cells was done using nucleofection, and 50% lethal concentration (LC(50)) of two small molecules was assessed using ATP-based cell viability assay. Apoptotic response was investigated in time course experiments with different apoptotic markers. Specificity of the small molecules was demonstrated by coimmunoprecipitation experiments for the lef-1/beta-catenin interaction. In vivo studies were done in JVM-3 subcutaneous xenograft model.
resultsInhibition of lef-1 by siRNA leads to increased apoptosis of CLL cells and inhibited proliferation of JVM-3 cell lines. The two small molecule inhibitors (CGP049090 and PKF115-584) efficiently kill CLL cells (LC(50)<1 microM), whereas normal B cells were not significantly affected. Coimmunoprecipitation showed a selective disruption of beta-catenin/lef-1 interaction. In vivo studies exhibited tumor inhibition of 69% with CGP049090 and 57% with PKF115-584 when compared with vehicle-treated controls, and the intervention was well tolerated.
conclusionsWe have demonstrated that targeting lef-1 is a new and selective therapeutic approach in CLL. CGP049090 or PKF115-584 may be attractive compounds for CLL and other malignancies that deserve further (pre)clinical evaluation.
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