Macrophage Polarization-Based Analysis of the Role of the FOXM1/KIF20A Axis in Breast Cancer Metastasis
摘要
To investigate the potential molecular processes underlying the function of forkhead box M1 (FOXM1)-mediated macrophage polarization in breast cancer (BC). The expression levels of Kinesin family member 20 A (KIF20A) and FOXM1 in BC tissues and tumor-associated macrophages (TAMs) were determined using RT-qPCR. Following co-culture of macrophages with BC cells, the impact of FOXM1 on the proliferation, invasive migration ability, and epithelial-mesenchymal transition (EMT) of BC cells was assessed using cell counting kit-8, Transwell, and Western blot assays respectively. Both the chromatin immunoprecipitation (ChIP) test and the dual luciferase reporter gene assay were used to confirm the connection between FOXM1 and KIF20A. Furthermore, the effect of FOXM1 on BC cell growth in vivo was evaluated via subcutaneous tumor formation assay conducted in nude mice. BC cell growth and metastasis were aided by M2 macrophage polarization. KIF20A and FOXM1 expression levels were markedly elevated in both TAMs and BC tissues. FOXM1 drived M2 polarization of macrophages by transcriptionally activating KIF20A. In vitro studies have demonstrated that FOXM1, through its regulation of KIF20A, enhanced BC cell proliferation, migration, invasion, and EMT. The upregulation of KIF20A expression by FOXM1 promotes M2 polarization of macrophages, thereby facilitating BC cell proliferation and metastasis.