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.

• Klíčová slova
• Breast cancer, IL1α, Inflammation, NF-κB, Transactivation, c-Myb,
• MeSH
• epitelo-mezenchymální tranzice MeSH
• interleukin-1alfa metabolismus   MeSH
• lidé MeSH
• mediátory zánětu metabolismus   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory prsu etiologie   metabolismus   patologie   MeSH
• NF-kappa B metabolismus   MeSH
• protoonkogenní proteiny c-myb metabolismus   MeSH
• sekvence aminokyselin MeSH
• signální transdukce * MeSH
• stres endoplazmatického retikula MeSH
• zánět genetika   metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• IL1A protein, human MeSH Prohlížeč
• interleukin-1alfa MeSH
• mediátory zánětu MeSH
• MYB protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• NF-kappa B MeSH
• protoonkogenní proteiny c-myb MeSH