Abstract P2-08-02: Novel tumor suppressor regulating the PI3K/AKT pathway in breast cancer

Abstract

Breast cancer affects approximately 1 in 8 women over the course of their lifetime. Of the many genes and pathways deregulated by this heterogeneous disease, alterations of members in the PI3K/AKT pathway are present in approximately 20% of all cases, making it one of the more frequently mutated pathways in breast cancer. The PI3K/AKT pathway is well known to be involved in essential cellular processes necessary for cancer development and progression, including altered proliferation, metabolism, and cell survival. Previous studies have made it well known that the activation of AKT is regulated through its phosphorylation, but recent studies have also shown that AKT can also be regulated via ubiquitination, leading to AKT hyperactivation. However, the mechanism and players involved in this process are not well understood. Better understanding of these pathways could inform on better potential therapeutics to target this disease. Recent work in our lab has identified GPS2, a member of the NCoR/SMRT complex, as a regulator of the insulin-signaling pathway through the inhibition of AKT ubiquitination by Ubc13. As many human cancers frequently have an increase in activated AKT, here we explore the potential of GPS2 as a tumor suppressor in the context of breast cancer and hope to elucidate the mechanism by which AKT ubiquitination regulates its activation. Citation Format: Chan S, Cardamone MD, Perissi V. Novel tumor suppressor regulating the PI3K/AKT pathway in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-08-02.