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- Title
Interleukin-6 Signaling in Triple Negative Breast Cancer Cells Elicits the Annexin A1/Formyl Peptide Receptor 1 Axis and Affects the Tumor Microenvironment.
- Authors
Vecchi, Lara; Mota, Sara Teixeira Soares; Zóia, Mariana Alves Pereira; Martins, Isabella Castro; de Souza, Jessica Brito; Santos, Tiago Góss; Beserra, Adriano de Oliveira; de Andrade, Victor Piana; Goulart, Luiz Ricardo; Araújo, Thaise Gonçalves
- Abstract
Annexin A1 (AnxA1) is a pleiotropic protein that exerts essential roles in breast cancer (BC) growth and aggressiveness. In our previous work, we described the autocrine signaling of AnxA1 through formyl peptide receptor 1 (FPR1) in the triple-negative (TN) BC cell line, MDA-MB-231. Here, we aimed to describe the interaction between the AnxA1/FPR1 and the Interleukin-6 (IL-6) signaling pathways and their role in the tumor microenvironment (TME). First, we demonstrated that AnxA1 and IL-6 expression levels are correlated in BC tissue samples. In three TNBC cell lines, overexpression of both AnxA1 and IL-6 was also identified. Next, we inhibited FPR1, the IL-6 receptor and STAT3 in both MDA-MB-231 and MDA-MB-157 cells. The FPR1 inhibition led to increased levels of IL-6 and secreted AnxA1 in both cell lines. On the other side, inhibition of the IL-6 receptor or STAT3 led to the impairment of AnxA1 secretion, suggesting the essential role of the IL-6 signaling cascade in the activation of the AnxA1/FPR1 autocrine axis. Finally, we described the interaction between IL-6 and the AnxA1/FPR1 pathways and their role on the TME by analyzing the effect of supernatants derived from MDA-MB-231 and MDA-MB-157 cells under the inhibition of FPR1 or IL-6 signaling on fibroblast cell motility.
- Subjects
TRIPLE-negative breast cancer; PEPTIDE receptors; ANNEXINS; TUMOR microenvironment; INTERLEUKIN-6
- Publication
Cells (2073-4409), 2022, Vol 11, Issue 10, p1705
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells11101705