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:Shi, M(legendsm01@163.com)
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
出版年:2018
DOI:10.1002/jcp.27863
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.
收录类别:SCOPUS
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85058036806&doi=10.1002%2fjcp.27863&partnerID=40&md5=32fe2ef36b2ca555b558f7683863e059
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