IDENTIFYING THE ONCOGENIC ROLE OF USP10 IN BREAST CANCER

Abstract

Ubiquitin-proteasome system (UPS) is known to regulate protein turnovers and have been implicated in various malignancies. Breast cancer is reported to be associated with deregulated post-translational modification of number of oncoproteins and tumor suppressor proteins such as c-MYC and PTEN, respectively. Using a genome wide functional RNAi screen, we identified USP10 as a novel deubiquitinase involved in stabilization of c-MYC and regulation of PI3K signaling pathway by inhibiting tumor suppressive function of PTEN. Furthermore, expression analysis of USP10 revealed significantly higher levels of USP10 in the breast cancer patients and its expression is positively correlated with the grade of breast cancer and negatively correlated with the poorer overall survival of the breast cancer patients. This study aims to provide a new insight for designing mechanism based cancer drugs and combination therapies in breast cancer patients with the loss of PTEN functionality and c-MYC stabilization.