期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 234, 期 7, 页码 12019-12028出版社
WILEY
DOI: 10.1002/jcp.27863
关键词
AKT; ESCC; GO-203; metabolism; MUC1-C; TIGAR
资金
- Natural Science Foundation of Shandong Province [2014ZRB14125]
- Key R&D Project of Shandong Province [2018GSF118123]
- Science and Technology development project of Shandong province [2014GSF118018, 2017GSF2018096]
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 ofglutathione 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 oftransmembrane 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.
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