RFC4 Promotes the Metastasis of Colorectal Cancer by Regulating the Wnt/β-Catenin Pathway

Replication factor C (RFC), a multimeric protein with ATPase activity, plays a crucial role in DNA replication and repair. RFC4, one of its subunits, is aberrantly expressed in various malignant tumors, including colorectal cancer (CRC). Nevertheless, the impact of RFC4 on CRC metastasis remains to be elucidated. In this study, we systematically examined the effects of RFC4 silencing on the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and Wnt/β-catenin signaling pathway in CRC cells in vitro. Additionally, we further explored the regulatory role of RFC4 in liver metastasis of CRC cells in vivo. Finally, BML-284, a known activator of the Wnt/β-catenin signaling pathway, was employed to validate the underlying mechanism by which RFC4 modulates the invasive phenotype of CRC cells. The results demonstrated that RFC4 was significantly overexpressed in CRC cell lines. Upon silencing of RFC4, the proliferation, migration, and invasion capabilities of CRC cells were markedly attenuated, and the EMT process as well as Wnt/β-catenin signaling pathway activity were effectively suppressed. Notably, RFC4 silencing significantly reduced liver metastasis of CRC cells in a nude mouse model. However, the inhibitory effects of RFC4 silencing on CRC cells proliferation, migration, invasion, and EMT were partially reversed by the intervention of the Wnt/β-catenin signaling pathway activator BML-284. Altogether, these results indicate that RFC4 plays a critical role in promoting CRC metastasis, and its mechanism of action may involve the regulation of Wnt/β-catenin signaling pathway activation to facilitate EMT.