ArticleGenes & cancer2010
Wnt/β-catenin Pathway Modulates the Sensitivity of the Mutant FLT3 Receptor Kinase Inhibitors in a GSK-3β Dependent Manner.
Article in Genes & cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Concomitant targeting of FLT3 and SPHK1 exerts synergistic cytotoxicity in FLT3-ITDCell communication and signaling : CCS · 2024Article
- Landscape of FLT3 Variations Associated with Structural and Functional Impact on Acute Myeloid Leukemia: A Computational Study.International journal of molecular sciences · 2024Article
- Histone Modification of Colorectal Cancer by Natural Products.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Concurrent Evaluation of the Expression and Methylation ofIranian journal of medical sciences · 2021Article
- Glycogen synthase kinase-3 and alternative splicing.Wiley interdisciplinary reviews. RNA · 2018Review
- Disruption of Wnt/β-Catenin Exerts Antileukemia Activity and Synergizes with FLT3 Inhibition inClinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- A Genome-Wide CRISPR Screen Identifies Genes Critical for Resistance to FLT3 Inhibitor AC220.Cancer research · 2017Article
- Aberrant activation of Wnt/β-catenin signaling drives proliferation of bone sarcoma cells.Oncotarget · 2015Article
- Pre-clinical efficacy of combined therapy with novel β-catenin antagonist BC2059 and histone deacetylase inhibitor against AML cells.Leukemia · 2015Article
- Wnt5A regulates ABCB1 expression in multidrug-resistant cancer cells through activation of the non-canonical PKA/β-catenin pathway.Oncotarget · 2014Article
- The E3 ubiquitin ligase TRAF6 inhibits LPS-induced AKT activation in FLT3-ITD-positive MV4-11 AML cells.Journal of cancer research and clinical oncology · 2013Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The FLT3 tyrosine kinase receptor is involved in both hematopoiesis and hematological malignancies. The Wnt/β-catenin pathway has been shown to participate in the self-renewal of hematopoietic stem cells and to cooperate with the mutant FLT3 receptors in leukemic transformation. However, the detailed biological impact of such a constitutively activated Wnt pathway remains to be further explored. Here, the authors report that activating mutations of FLT3 constitutively activate β-catenin by inhibition of GSK-3β in a PI3 kinase pathway-dependent manner. Ectopic expression of a dominant negative form of GSK-3β in FLT3-ITD-expressing cells activated β-catenin and blocked the downregulation of the TCF/β-catenin transcriptional activity induced by inhibition of FLT3 kinase. Furthermore, inhibition of cell proliferation and colony formation induced by such suppression of FLT3 kinase activity could be partially reversed by knockdown of GSK-3β and restored by knockdown of either TCF4 or β-catenin. Moreover, exogenous activation of the Wnt pathway also attenuated such inhibitory effect. These findings indicate that the potencies of the inhibitors of FLT3 kinase activity could be modulated by the activity of the Wnt/β-catenin pathway in the cells harboring FLT3-ITD mutations, and FLT3-ITDs signal through GSK-3β to activate β-catenin that this is likely to directly contribute to the leukemic phenotype.
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Registered trials
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