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• W2893312319 abstract "To improve cancer patient outcome significantly, we must understand the mechanisms regulating stem-like cancer cells, which have been implicated as a cause of metastasis and treatment resistance. The transcription factor C/EBPδ can exhibit pro- and anti-tumorigenic activities, but the mechanisms underlying the complexity of its functions are poorly understood. Here we identify a role for breast cancer cell intrinsic C/EBPδ in promoting phenotypes that have been associated with cancer stem cells (CSCs). While C/EBPδ expression is not abundant in most metastatic breast cancers, our data support a pro-tumorigenic role of C/EBPδ when expressed in subsets of tumor cells and/or through transient activation by the tumor microenvironment or loss of substrate adhesion. Using genetic mouse models and human breast cancer cell lines, we show that deletion or depletion of C/EBPδ reduced expression of stem cell factors and stemnness markers, sphere formation and self-renewal, along with growth of tumors and established experimental metastases in vivo. C/EBPδ is also known as a mediator of the innate immune response, which is enhanced by hypoxia and interleukin-6 (IL-6) signaling, two conditions that also play important roles in cancer progression. Our mechanistic data reveal C/EBPδ as a link that engages two positive feedback loops, in part by directly targeting the IL-6 receptor (IL6RA) gene, and, thus, amplifying IL-6 and HIF-1 signaling. This study provides a molecular mechanism for the synergism of tumor microenvironmental conditions in cancer progression with potential implications for the targeting of CSCs." @default.
• W2893312319 created "2018-10-05" @default.
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• W2893312319 date "2018-09-27" @default.
• W2893312319 modified "2023-10-15" @default.
• W2893312319 title "C/EBPδ links IL-6 and HIF-1 signaling to promote breast cancer stem cell-associated phenotypes" @default.
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• W2893312319 doi "https://doi.org/10.1038/s41388-018-0516-5" @default.
• W2893312319 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6437025" @default.
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• W2893312319 hasPublicationYear "2018" @default.
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