FOXI3 promotes migration and proliferation in prostate cancer bone metastases, modulated by FGF8.

Studies have shown that all men who die from prostate cancer exhibit bone involvement, highlighting the clinical significance of bone metastases. Previously, we demonstrated that prostate cancer exhibits elevated expression of FOXI3; a transcription factor critical to bone development. However, its functional role in prostate cancer progression remains unexplored. In this study, we explored FOXI3 expression in human prostate cancer tissues and cell lines. Immunohistochemical analysis revealed a significant association between FOXI3 expression, tumor pathology, and increasing tumor grade. Analysis of publicly available gene expression data from prostate cancer patients showed that FOXI3 is markedly elevated in bone metastases and strongly correlates with FGF8, suggesting a potential bone-specific regulatory interaction between these factors. Consistent with this, treatment of bone-derived prostate cancer cells with FGF8 increased FOXI3 RNA expression, whereas no such effect was observed in a brain-metastatic cell line. Further, we demonstrated that the FGF8-FOXI3 axis regulates bone-derived prostate cancer cell migration and proliferation in a FOXI3 dependent manner. Together, our findings demonstrate a pro-metastatic role of FOXI3 in prostate cancer progression.