c-Myb interferes with inflammatory IL1α-NF-κB pathway in breast cancer cells.

Autor:	Dúcka M; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic; International Clinical Research Center, Center for Biological and Cellular Engineering, St. Anne's University Hospital, Brno, Czech Republic., Kučeríková M; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic., Trčka F; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic; International Clinical Research Center, Center for Biological and Cellular Engineering, St. Anne's University Hospital, Brno, Czech Republic., Červinka J; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic; International Clinical Research Center, Center for Biological and Cellular Engineering, St. Anne's University Hospital, Brno, Czech Republic., Biglieri E; Institute of Physiology, University of Zurich and Comprehensive Cancer Center, Zurich, Switzerland., Šmarda J; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic., Borsig L; Institute of Physiology, University of Zurich and Comprehensive Cancer Center, Zurich, Switzerland., Beneš P; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic; International Clinical Research Center, Center for Biological and Cellular Engineering, St. Anne's University Hospital, Brno, Czech Republic., Knopfová L; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic; International Clinical Research Center, Center for Biological and Cellular Engineering, St. Anne's University Hospital, Brno, Czech Republic. Electronic address: knopfova@sci.muni.cz.
Jazyk:	angličtina
Zdroj:	Neoplasia (New York, N.Y.) [Neoplasia] 2021 Mar; Vol. 23 (3), pp. 326-336. Date of Electronic Publication: 2021 Feb 20.
DOI:	10.1016/j.neo.2021.01.002
Abstrakt:	The transcription factor c-Myb can be involved in the activation of many genes with protumorigenic function; however, its role in breast cancer (BC) development is still under discussion. c-Myb is considered as a tumor-promoting factor in the early phases of BC, on the other hand, its expression in BC patients relates to a good prognosis. Previously, we have shown that c-Myb controls the capacity of BC cells to form spontaneous lung metastasis. Reduced seeding of BC cells to the lungs is linked to high expression of c-Myb and a decline in expression of a specific set of inflammatory genes. Here, we unraveled a c-Myb-IL1α-NF-κB signaling axis that takes place in tumor cells. We report that an overexpression of c-Myb interfered with the activity of NF-κB in several BC cell lines. We identified IL1α to be essential for this interference since it was abrogated in the IL1α-deficient cells. Overexpression of IL1α, as well as addition of recombinant IL1α protein, activated NF-κB signaling and restored expression of the inflammatory signature genes suppressed by c-Myb. The endogenous levels of c-Myb negatively correlated with IL1α on both transcriptional and protein levels across BC cell lines. We concluded that inhibition of IL1α expression by c-Myb reduces NF-κB activity and disconnects the inflammatory circuit, a potentially targetable mechanism to mimic the antimetastatic effect of c-Myb with therapeutic perspective. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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