Objective To explore the function and mechanism of cleavage and polyadenylation factor 6 (CPSF6) in breast cancer bone metastasis.

Methods The expression of CPSF6 was analyzed in 12 patients with bone metastasis of breast cancer and 20 patients with primary breast cancer by real-time fluorescent quantitative PCR (RT-qRCR), Western blotting (WB) and immunohistochemical staining (IHC). To explore the effect of CPSF6 on the growth and metastatic ability of tumor cells through cell experiments. To explore the effect of CPSF6 knockout on bone metastatic ability of breast cancer cells by in vivo metastasis model. To further explore the ability of breast cancer cells to reshape the extracellular microenvironment through CPSF6, and to examine the regulatory effect of CPSF6 on downstream target genes.

Results The expression level of CPSF6 in metastatic foci of breast cancer patients was significantly increased. CPSF6 is positively correlated with the proliferation and migration of breast cancer cells. After knocking down CPSF6 in 231-BM cells, the supernatant secreted by CPSF6 decreased the ability of osteoclast progenitor cells to differentiate into mature cells, and the number of osteoclasts around the metastatic focus decreased significantly in vivo. Knock-down CPSF6 can down-regulate the expression of Notch pathway ligand JAG1 in tumor cells, which leads to the inactivation of Notch pathway and inhibition of downstream target genes in osteoclast progenitor cells in microenvironment.

Conclusion CPSF6 is highly expressed in bone metastatic foci. CPSF6 promotes the maturation rate and osteolytic activity of osteoclasts around tumor tissues by regulating the Notch signaling pathway, thus promoting the osteolytic bone metastasis of breast cancer.