秦正红教授在Cancer Research上发表题为TIGAR Has a Dual Role in Cancer Cell Survival through 3 Regulating Apoptosis and Autophagy的论文。
Abstract: The p53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis, resulting in higher intracellular 8 NADPH, lower reactive oxygen species (ROS) and autophagy activity. In this study, we investigated whether 9 TIGAR might exert dual impacts on cancer cell survival based on its ability to inhibit both apoptosis and 10 autophagy. In liver or lung cancer cells treated with the anticancer drug epirubicin, TIGAR levels increased in a 11 dose- and time-dependent manner. TIGAR silencing enhanced epirubicin-induced elevations in ROS levels and 12 apoptosis rates, in a manner that was blocked by ectopic addition of NADPH or N-acetyl cysteine. These findings 13 were correlated with reduced tumorigenicity and increased chemosensitivity in mouse xenograft tumor assays. In 14 parallel, TIGAR silencing also enhanced the epirubicin-induced activation of autophagy, in a manner that was also 15 blocked by ectopic addition of NADPH. Notably, TIGAR silencing also licensed epirubicin-mediated inactivation 16 of the mTOR pathway, suggesting TIGAR also exerted a negative impact on autophagy. However, genetic or 17 pharmacologic inhibition of autophagy increased epirubicin-induced apoptosis in TIGAR-silenced cells. Overall, 18 our results revealed that TIGAR inhibits both apoptosis and autophagy, resulting in a dual impact on tumor cell 19 survival in response to tumor chemotherapy.
