The potential pathway of FOXC1 high expression in regulating the proliferation, migration, cell cycle and epithelial-mesenchymal transition of basal-like breast cancer and in vivo imaging

Purpose: To investigate the role of high forkhead box C1 (FOXC1) expression in basal-like breast cancer (BLBC) cells in vitro and in vivo, as well as its potential regulatory pathway. Methods: Stable MDA-MB-231 cells, a type of BLBC cells, with high FOXC1 expression and luciferase (FOXC1) were established. The parental MDA-MB-231 cells with luciferase served as the control group. Proliferation, migratory capabilities and the cell cycle were evaluated. The tumorigenicity and the spontaneous pulmonary metastasis were measured in mice in viva In vivo imaging was also performed. Histo-pathology, immunohistochemical analysis and microarray processing were evaluated. Paired Student's t-test was used. Results: The proliferation and migratory ability of FOXClMDA-MB-231 cells were enhanced significantly (p<0.05). Spontaneous pulmonary metastases were observed in 2 out of 5 mice, but no pulmonary metastases were observed in control animals. There were more FOXC1 cells in the GI phase compared to the control (p<0.05), but there were also significant reductions of cells in the S and G2 phases (p<0.05). The CD31 and endoglin (CD105) expression in the FOXC1 tumor was higher than in the control, especially CD105 (p<0.05). The total fluorescence expression quantity of FOXCI was higher than in the control cells (p<0.05), and the apparent diffusion coefficient (ADC) values were lower compared with the control (p<0.05). One pathway with the most gene enrichment (p38 MAPK signalling) may play a key role in regulating BLBC cell proliferation, migration, cell cycle and epithelial-mesenchymal transition (EMT) through the interaction of related critical regulatory genes (IL-6 and FOXC1). Conclusion: High FOXC1 enhanced the proliferation, migratory ability and EMT of BLBC cells. This function may be regulated by IL-6 and FOXC1 through the p38 MAPK signalling pathway.