SLC1A5 regulates cell proliferation and self-renewal through β-catenin pathway mediated by redox signaling in arsenic-treated uroepithelial cells

Arsenic exposure increases the risk of bladder cancer in humans, but its underlying mechanisms remain elusive. The alanine, serine, cysteine-preferring transporter 2 (ASCT2, SLC1A5) is frequently overexpressed in cancer cells. The aim of this study was to evaluate the effects of arsenic on SLC1A5, and to determine the role of SLC1A5 in the proliferation and self-renewal of uroepithelial cells. F344 rats were exposed to 87 mg/L NaAsO2 or 200 mg/L DMAV for 12 weeks. The SV-40 immortalized human uroepithelial (SV-HUC-1) cells were cultured in medium containing 0.5 μM NaAsO2 for 40 weeks. Arsenic increased the expression levels of SLC1A5 and β-catenin both in vivo and in vitro. SLC1A5 promoted cell proliferation and self-renewal by activating β-catenin, which in turn was dependent on maintaining GSH/ROS homeostasis. Our results suggest that SLC1A5 is a potential therapeutic target for arsenic-induced proliferation and self-renewal of uroepithelial cells.