Interleukin-6 Signaling in Triple Negative Breast Cancer Cells Elicits the Annexin A1/Formyl Peptide Receptor 1 Axis and Affects the Tumor Microenvironment

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 10; p. 1705
• Main 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20-05-2022; MDPI
• Subjects: Annexin A1; Antibodies; autocrine signaling; Autocrine signalling; Breast cancer; Fibroblasts; formyl peptide receptor; Genotype & phenotype; IL-6; Interleukin 6; Interleukin 6 receptors; Medical prognosis; Medical research; Metastasis; Peptides; Proteins; Signal transduction; STAT3; Stat3 protein; Tumor microenvironment; Tumors; United States > US; breast cancer; formyl peptide receptor; autocrine signaling; Annexin A1; IL-6; STAT3
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11101705

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.