Abstract 3542: Missense mutations in USE1 promote lung tumorigenesis

Abstract

Abstract The UBA6-USE1 enzyme cascade is a poorly characterized arm of the ubiquitin-proteasome system. We found that UBA6 and USE1 proteins are frequently overexpressed in lung cancer patients (83.01% and 92.45%, respectively; n = 106). Stable overexpression of UBA6 or USE1 significantly increased cell proliferation, migration, and invasiveness in lung cancer cells and xenograft models, whereas their knockdown significantly reduced cell proliferation, migration, and invasion. USE1 has a conserved D-box domain and the level of the protein was regulated by the anaphase-promoting complex through its interaction with CDC20 and CDH1. Furthermore, several missense mutations in USE1 identified in patients prolong the half-life and stability of the protein. Our findings reveal novel roles for USE1 in lung cancer and the possible use of USE1 as a novel biomarker and therapeutic target for lung cancer treatment. Citation Format: Peter C. W. Lee. Missense mutations in USE1 promote lung tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3542.