Abstract 4312: Targeting FoxM1 in inducing anticancer effects in triple-negative breast cancer cells

Abstract

Abstract Triple-negative breast cancer (TNBC) is highly aggressive and a major threat to survival due to absence of molecular targets. Invasion, metastasis and chemoresistance are the greatest obstacles to the successful tumor treatment in breast cancer patients. In this study, over-expression of Forkhead box transcription factor M1 (FoxM1) was observed in 79% (770/975) of breast cancers from Saudi Arabia. FoxM1 over-expression was found to be an independent prognostic marker in multivariate analysis in late stage (Stage 3 and 4) breast cancer (p=0.0110). Our in vitro results show that treatment with thiostrepton, a dual FoxM1 and proteasome inhibitor caused cell viability loss and induce apoptosis in a dose dependent manner in triple-negative breast cancer cell lines. Thiostrepton treatment also inhibited colony formation and invasion/migration capabilities of triple-negative breast cancer cells. In vivo, thiostrepton treatment regressed TNBC cells; MDA-MB-231 generated xenografts via down-regulation of FoxM1 and its downstream targets. Altogether, our results suggest that FoxM1 and its associated signaling pathway may be a potential target for therapeutic intervention in the treatment of aggressive breast cancer. Key words: Triple-negative breast cancer, FoxM1, Apoptosis and Invasion Citation Format: Rong Bu, Abdul K. Siraj, Maqbool Ahmed, Fouad Al-Dayel, Khawla S. Al-Kuraya. Targeting FoxM1 in inducing anticancer effects in triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4312. doi:10.1158/1538-7445.AM2017-4312