SCFFBXO22 targets HDM2 for degradation and modulates breast cancer cell invasion and metastasis

Overexpression of human homologue of mouse double minute 2 (HDM2) is associated with aggressive cancer malignancy. It is therefore critical to understand cellular mechanisms for the control of HDM2 abundance. By identifying Skp1-Cullin 1-FBXO22-ROC1 (SCF^FBXO22) as an E3 ubiquitin ligase for HDM2, our work has significantly improved knowledge of the cellular regulatory network required for the maintenance of HDM2 protein stability. The results of tumor cell invasion, mouse 4T1 breast tumor model study, and human breast cancer tissue expression analyses suggest a role for SCF^FBXO22 in the inhibition of breast cancer metastasis by down-regulating HDM2.