Upregulation of FOXP4 in breast cancer promotes migration and invasion through facilitating EMT

Tao Ma,1–4 Jin Zhang1–4 1The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, P.R. China; 2Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, P.R. China; 3Key Laboratory of Cancer Prevention and Therapy, Tianjin, P.R. China; 4Tianjin’s Clinical Research Center for Cancer, Tianjin, P.R. China Background: Family of forkhead box transcription factors has been found to play key roles in multiple types of cancer. Materials and methods: Our study is to decipher the effects of FOXP4 in human breast cancer (BC). Quantitative real-time polymerase chain reaction and Western blot analyses were performed to determine the mRNA and protein expressions of FOXP4 in BC tissue samples and cell lines. The gain and loss of function assay were used to explore the detailed roles of FOXP4 in breast cell lines, including MDA-MB-231 and MCF-7 cells. Its effect on BC growth, migration, and invasion were evaluated by colony formation assay, CCK-8 assay, wound-healing assay, and transwell invasion assay, respectively. Results: Our findings revealed that FOXP4 promotes cell proliferation, migration, as well as invasion of BC cells. Furthermore, FOXP4 also facilitates epithelial–mesenchymal transition. ChIP, qChIP assay, and dual luciferase reporter assay were used to examine whether Snail is a downstream target of FOXP4. Moreover, overexpression of Snail could partially rescue the effects of FOXP4 inhibition on cancer cell migration and invasion. Conclusion: Our findings revealed that FOXP4 is a critical regulator in BC. Keywords: FOXP4, EMT, Snail, migration, breast cancer