Abstract 71: NEDD8-activating enzyme inhibitor MLN4924 reduces cell viability and induces apoptosis in chemoresistant cancer stem-like cells of human urothelial carcinomas in vitro and in vivo

Abstract

Abstract Emerging evidence indicates that cancer stem cells (CSCs) may play a crucial role in cancer tumorigenesis, metastasis, and drug resistance. To develop treatment to inhibit CSCs provides promising target for cancer therapy. In this study, we identified a subpopulation of chemoresistant cancer stem-like cells of UCs (T24/R) after chemotherapeutic drug selection from T24, a bladder UC cell line. The T24/R cells displayed stemness markers (SOX2, Nanog, and Kruppel-like factor 4), high tumorigenicity in vivo, and enhanced invasion ability because of their epithelial-mesenchymal transition (EMT) properties. A neddylation inhibitor, MLN4924, efficiently inhibited viability and migration as well as induced apoptosis in the T24/R cells with concomitant suppression of stemness and EMT markers. Our findings suggest that MLN4924 effeiciently suppressed chemoresistant cancer stem-like UC cells and was a promising agent to conquer drug resistance in human bladder UCs. Citation Format: Shih-Ming Liao, Fu-Shun Hsu, Shao-Ping Yang, Yu-Wei Chang, Po-Ming Chow, Yeong-Shiau Pu, Yu-Chieh Tsai, Kuan-Lin Kuo, Kuo-How Huang. NEDD8-activating enzyme inhibitor MLN4924 reduces cell viability and induces apoptosis in chemoresistant cancer stem-like cells of human urothelial carcinomas in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 71.