In the 4T1 murine TNBC model, we observed that the increased CDC73 protein level in Ubr5−/− cells leads to significant reduction on both tumor growth and metastasis, and this phenotype can be almost fully reversed to the WT when Cdc73 was further knocked down, via the mechanism of regulating CD8+ T cells infiltration and apoptosis in TME and inhibiting the expression of β-catenin and E-cadherin, respectively. The gene discussed is UBR5; the disease is neoplasm.