Publication details
c-Myb interferes with inflammatory IL1alpha-NF-kappaB pathway in breast cancer cells
| Authors | |
|---|---|
| Year of publication | 2021 |
| Type | Article in Periodical |
| Magazine / Source | Neoplasia |
| MU Faculty or unit | |
| Citation | |
| Web | https://doi.org/10.1016/j.neo.2021.01.002 |
| Doi | http://dx.doi.org/10.1016/j.neo.2021.01.002 |
| Keywords | Breast cancer; c-Myb; IL1alpha; NF-kappaB; Inflammation; Transactivation |
| Description | 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-IL1alpha-NF-kappaB signaling axis that takes place in tumor cells. We report that an overexpression of c-Myb interfered with the activity of NF-kappaB in several BC cell lines. We identified IL1alpha to be essential for this interference since it was abrogated in the IL1alpha-deficient cells. Overexpression of IL1alpha, as well as addition of recombinant IL1alpha protein, activated NF-kappaB signaling and restored expression of the inflammatory signature genes suppressed by c-Myb. The endogenous levels of c-Myb negatively correlated with IL1alpha on both transcriptional and protein levels across BC cell lines. We concluded that inhibition of IL1alpha expression by c-Myb reduces NF-kappaB activity and disconnects the inflammatory circuit, a potentially targetable mechanism to mimic the antimetastatic effect of c-Myb with therapeutic perspective. |
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