Epithelial-mesenchymal transition (EMT) is critical for the conversion of early stage tumors into invasive malignancies.Emerging evidence suggests that aberrant epigenetic modifications contribute significantly to epithelial-mesenchymal transition and cancer metastasis.RNF8 is an ubiquitin E3 ligase with C-terminal RING domain,and plays essential roles in DNA damage response and spermatogenesis through RNF8 mediated ubiquitination of histone.However,the role of RNF8 in the pathogenesis of breast cancer is unclear.Here,we identify RNF8 as a novel factor involved in EMT and breast cancer metastasis.RNF8 is overexpressed in highly metastatic breast cell lines.Overexpression of RNF8 in MCF-7 induces EMT and promotes cell migration.On the contrary,silencing of RNF8 in MDA-MB-231 induces MET phenotypes,inhibits cell migration and reduces tumor metastasis in nude mice xenografi model.Importantly,the expression of RNF8 is up-regulated in breast cancers tissues and is positively correlates with lymph node metastasis and inversely correlates with survival time of the patients.Mechanistic investigations reveal that the metastatic promoting effects of RNF8 in breast cancer was associated with the inactivation of GSK-3β and activation of β-catenin signaling.Taken together,our results establish an important role for RNF8 in breast cancer progression,and suggest that RNF8 could be used as a potential therapeutic target for the prevention and treatment of breast cancer.