标题：Inhibition of MUC1-C regulates metabolism by AKT pathway in esophageal squamous cell carcinoma
作者：GongSun X.; Zhao Y.; Jiang B.; Xin Z.; Shi M.; Song L.; Qin Q.; Wang Q.;等
作者机构：[GongSun, X] Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China;[ Zhao, Y] Departm 更多
通讯作者地址：[Shi, M] Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong UniversityChina;
来源：Journal of Cellular Physiology
关键词：AKT; ESCC; GO-203; metabolism; MUC1-C; TIGAR
摘要：Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive tumors worldwide. The Mucin 1 (MUC1) heterodimeric protein has been confirmed that is overexpressed in ESCC and induced adverse outcomes. However, the detailed mechanism(s) remained challenging. So, we investigated the relationship between MUC1-C and metabolism in ESCC cells. In the results, TP53-induced glycolysis and apoptosis regulator (TIGAR) was overexpressed and correlative with MUC1-C positively in ESCC tissue. Targeting MUC1-C inhibits AKT–mTORC–S6K1 signaling and blocks TIGAR translation. We found that the inhibitory effect of GO-203 on TIGAR was mediated by inhibition of AKT–mTOR–S6K1 pathway. The findings also demonstrated that the suppressive effect of GO-203 on TIGAR is related to the decrease of glutathione level, the increase of reactive oxygen species and the loss of mitochondrial transmembrane membrane potential. In xenograft tissues, GO-203 inhibited the growth of ESCC cells and lead to the low expression of transmembrane C-terminal subunit (MUC1-C) and TIGAR. This evidence supports the contention that MUC1-C is significant for metabolism in ESCC and indicated that MUC1-C is a potential target for the treatment of ESCC. © 2018 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.