β-Catenin and NF-κB co-activation triggered by TLR3 stimulation facilitates stem cell-like phenotypes in breast cancer
| Autor: | D Jia, L Chi, Daniel Figeys, S Ooi, L G Filion, W Yang, Y Tan, H Liu, Lisheng Wang, L Li |
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| Rok vydání: | 2014 |
| Předmět: |
Beta-catenin
Mice Nude Breast Neoplasms Tumor initiation Biology Chalcones Cancer stem cell Cell Line Tumor medicine Animals Humans Molecular Biology beta Catenin Original Paper NF-kappa B Cancer Cell Biology medicine.disease 3. Good health Toll-Like Receptor 3 Disease Models Animal Phenotype Catenin Immunology Cancer cell Cancer research biology.protein Neoplastic Stem Cells Female Signal transduction Stem cell Neoplasm Transplantation Signal Transduction |
| Zdroj: | Cell Death and Differentiation |
| ISSN: | 1476-5403 |
| Popis: | Cancer stem cells (CSCs) are responsible for tumor initiation and progression. Toll-like receptors (TLRs) are highly expressed in cancer cells and associated with poor prognosis. However, a linkage between CSCs and TLRs is unclear, and potential intervention strategies to prevent TLR stimulation-induced CSC formation and underlying mechanisms are lacking. Here, we demonstrate that stimulation of toll-like receptor 3 (TLR3) promotes breast cancer cells toward a CSC phenotype in vitro and in vivo. Importantly, conventional NF-κB signaling pathway is not exclusively responsible for TLR3 activation-enriched CSCs. Intriguingly, simultaneous activation of both β-catenin and NF-κB signaling pathways, but neither alone, is required for the enhanced CSC phenotypes. We have further identified a small molecule cardamonin that can concurrently inhibit β-catenin and NF-κB signals. Cardamonin is capable of effectively abolishing TLR3 activation-enhanced CSC phenotypes in vitro and successfully controlling TLR3 stimulation-induced tumor growth in human breast cancer xenografts. These findings may provide a foundation for developing new strategies to prevent the induction of CSCs during cancer therapies. |
| Databáze: | OpenAIRE |
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