Fig. 6

A schematic diagram of the molecular mechanism by which IL-6 secreted by breast cancer upregulates KDM2A in mammary fibroblast that can promote M2 macrophage polarization and increase paclitaxel resistance. Breast cancer cells secret IL-6, which triggers the activation of STAT3 in mammary fibroblasts. Active STAT3 then forms a complex with NFκB p50 and binds to the -154 bp to -144 bp region of the KDM2A promoter, leading to increased KDM2A expression in these fibroblasts. Elevated KDM2A levels in fibroblasts result in the release of CXCR2-assocciated chemokines, which stimulate the polarization of M2 macrophages via the CXCR2 signaling pathway. Finally, M2 macrophage release CCL2, contributing to increase resistance of breast cancer to paclitaxel. The mechanism highlights potential targets for therapeutic intervention in paclitaxel-resistant breast cancer