Farnesyltransferase Inhibitor (R115777) Targets CENPF to Inhibit Breast Cancer Bone Metastasis by Regulating the PI3k/AKT/mTOR/PTHrP Pathway.

Background: Farnesyltransferase inhibitor R115777 has shown promising antitumor effects in various types of cancer by targeting RAS proteins and CENPF farnesylation. To explore its potential in breast cancer (BC), In our study, we aimed to uncover its specific efficacy and underlying mechanisms.

Methods: Through knockdown experiments, we observed that inhibiting CENPF effectively suppressed the growth and metastasis of BC cells, both in vitro and in vivo.

Results: Remarkably, R115777 displayed a selective affinity for CENPF, leading to the inhibition of its-mediated proliferation and bone metastasis in BC cells. Further investigation unveiled that this inhibitory effect was linked to the activation of the PI3K-AKT-mTOR signaling pathway by R115777. Consequently, the secretion of parathyroid hormone-related peptide (PTHrP), a factor crucial for bone marrow development, was detected and inhibited by R115777. As a result, this cascade of events significantly impeded bone metastasis in BC.

Conclusion: Our findings highlight the potential of R115777 as a novel therapeutic strategy for preventing bone metastasis in breast cancer. By specifically targeting CENPF and modulating the PI3K-AKT-mTORC1 pathway, R115777 emerges as a promising targeted treatment option in combating the progression and metastasis of breast cancer.