Abstract 3784: The role of the taurine transporter SLC6A6 in promoting prosurvival activity and multidrug resistance of colorectal cancer

Abstract

Abstract The identification of a novel therapeutic target is desired to improve the treatment of colorectal cancer (CRC). In a comprehensive gene expression analysis, we found that the taurine transporter SLC6A6 was highly expressed in CRC. In the functional analysis, SLC6A6-knocked down (KD) CRC cells showed attenuated cell-survival activity accompanying enhanced sensitivity of the drugs (5-FU, DOX and SN-38). Moreover, the number of side population (SP) cells and their cancer stem cell (CSC)-like properties such as tumor-initiation were abrogated by SLC6A6-KD. Conversely, increased the cell-survival activity, the fraction of SP cells and enhancement of multidrug resistance (MDR) were observed in SLC6A6-overexpressed cells. Furthermore, SLC6A6-siRNA treatment enhanced the cytotoxic effect of all 3 drugs as distinct from ABCG2-siRNA treatment, the efficacy of which was limited to its 2 substrate-drug, DOX and SN-38. Finally, we clarified the prosurvival and anti-apoptotic effects of the taurine transporter SLC6A6 in CRC cells. Moreover, we found that SLC6A6 plays an important role in the maintenance of CSC characteristics promoting cell survival signal and MDR. Our findings indicate that the SLC6A6 may be a novel therapeutic target for refractory CRC. Citation Format: Masahiro Yasunaga, Yasuhiro Matsumura. The role of the taurine transporter SLC6A6 in promoting prosurvival activity and multidrug resistance of colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3784.