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• W2907191569 endingPage "611" @default.
• W2907191569 startingPage "598" @default.
• W2907191569 abstract "The Inhibitor of Nuclear Factor Kappa B Kinase Subunit Epsilon (IKKε) is an oncogenic protein that is up-regulated in various types of human cancers, including breast tumors. This kinase regulates diverse processes associated with malignant progression including proliferation, invasion, and metastasis. To delve into the molecular mechanisms regulated by this kinase we performed RNA-seq and network analysis of breast cancer cells overexpressing IKKε. We found that the TNF/NF-κB cascade was clearly enriched, and in accordance, NF-κB pathway inhibition in these cells resulted in a decreased expression of IKKε target genes. Interestingly, we also found an enrichment of a mammary stemness functional pathway. Upregulation of IKKε led to an increase of a stem CD44+/CD24−/low population accompanied by a high expression of stem markers such as ALDH1A3, NANOG, and KLF4 and with an increased clonogenic ability and mammosphere formation capacity. These results were corroborated with in vivo dilution assays in zebrafish embryos which showed a significant increase in the number of Cancer Stem Cells (CSCs). Finally, we found that Triple-Negative breast tumors, which are enriched in CSCs, display higher levels of IKKε than other breast tumors, supporting the association of this kinase with the stem phenotype. In conclusion, our results highlight the role of IKKε kinase in the regulation of the stem cell phenotype in breast cancer cells, as assessed by expression, functional and in vivo assays. These results add to the potential use of this kinase as a therapeutic target in this neoplasia." @default.
• W2907191569 created "2019-01-11" @default.
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• W2907191569 date "2019-04-01" @default.
• W2907191569 modified "2023-10-17" @default.
• W2907191569 title "IKKε regulates the breast cancer stem cell phenotype" @default.
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• W2907191569 doi "https://doi.org/10.1016/j.bbamcr.2019.01.002" @default.
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• W2907191569 hasPublicationYear "2019" @default.
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