Abstract LB-250: Induction of c-Cbl is a novel mechanism for the anti-cancer effect of HDAC inhibitor in lung cancer

Abstract

Abstract Here we found loss of c-Cbl, an E3 ligase, expression in Non-small cell lung cancer (NSCLC) compared with its adjacent normal tissue in patient specimens. HDAC inhibition by WJ or knockdown of HDAC 1, HDAC2, HDAC3 or HDAC6 all induced c-Cbl. Ectopic expression of c-Cbl induced decreased EGFR, inhibited growth in NSCLC cells. Knockdown of EGFR inhibited NSCLC growth. Mutation of EGFR at Y1045 decreased WJ-induced growth inhibition as well as in vivo anti-cancer effect and EGFR degradation mediated by WJ. Time-lapse confocal analysis showed co-localization of c-Cbl and EGFR after WJ treatment. Furthermore, WJ inhibited lung tumor growth through c-Cbl induction in orthotopic and tail vein injected models. C-Cbl up-regulation induced by HDACi is a potential strategy for NSCLC treatment. Citation Format: Chen Ching-Chow, Tzu-Tang Wei, Yu-Chin Lin, Pei-Hua Lin, Jin-Yuan Shih, Chia-Wei Chou. Induction of c-Cbl is a novel mechanism for the anti-cancer effect of HDAC inhibitor in lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-250. doi:10.1158/1538-7445.AM2015-LB-250