NCoA3 upregulation in breast cancer-associated adipocytes elicits an inflammatory profile

Purpose NCoA3 is a transcriptional coactivator of NF-κB and other factors, present in undetectable levels into normal cells and amplified or overexpressed in several types of cancer, including breast tumors. We have previously demonstrated that NCoA3 levels decrease during adipogenesis, but its role in tumor-surrounding adipose tissue is still unknown. Therefore, in this work, we studied the modulation of NCoA3 in breast cancer-associated adipocytes and evaluated its correlation with the expression of inflammatory markers. Methods We collected mammary adipose tissue (MAT) from female mice that were stimulated with conditioned media from breast cancer cell lines or MAT adjacent to tumors from breast cancer patients. Then, the expression levels of NCoA3 were evaluated by qPCR and immunohistochemistry. TNF and MCP1 levels were measured. Ex vivo models were validated using 3T3-L1 cell lines and bioinformatics analysis. Results We found that in MAT samples expressing high levels of NCoA3 were mainly associated to a pro-inflammatory profile. Even more, patients with a worse prognosis and advanced clinical stage of disease showed high levels of this coactivator. Furthermore, in 3T3-L1 cell line-derived adipocytes, NCoA3 silencing or NF-κB inhibition reverted the expression of inflammatory molecules. Conclusion The modulation of NCoA3 levels in synergy with NF-κB activity in MAT in tumoral context, could be determinant factors to establish breast cancer-associated inflammation. As adipocytes are involved in the development and progression of breast cancer, this signaling network deserves to be further investigated to improve future tumoral treatments.