Deubiquitination and stabilization of estrogen receptor α by ubiquitin-specific protease 7 promotes breast tumorigenesis

Breast cancer is the most common malignancy in women around the world. Estrogen receptor alpha (ER alpha) is expressed in approximately 70% of breast tumors, and considered as one of most effective targets in breast cancer therapy. It has been reported that the degradation of ER alpha protein is mediated by ubiquitin-proteasome system. However, little is known about the regulation of ER alpha deubiquitination, a critical constituent of its degradation Control. The current study first reports that there is a positive correlation between ER alpha and ubiquitin specific protease 7 (USP7) protein levels in human breast tumor tissues. Subsequent studies showed that USP7 physically interacted with the ER alpha, thereby mediating the deubiquitination and stabilization of ER alpha. In addition, USP7 inhibition or silencing led to growth inhibition and apoptosis of ER alpha-positive breast cancer cells both in vitro and in vivo. Furthermore, overexpression of ER alpha rescued the USP7 silencing-induced cell cycle arrest and apoptosis, supporting that ER alpha status is essential to the function of USP7 in breast carcinogenesis. Overall, this study suggests that targeting USP7-ER alpha complex could be a potential strategy to treat ER alpha-positive breast cancer.