期刊
AUTOPHAGY
卷 9, 期 7, 页码 1057-1068出版社
LANDES BIOSCIENCE
DOI: 10.4161/auto.24632
关键词
salinomycin; endoplasmic reticulum stress; MTOR; autophagy; apoptosis
类别
资金
- National Natural Science Foundation of China [31171332, 81000947]
- Program for New Century Excellent Talents in University [NCET-10-0521]
- National Key Basic Research Program of China [2013CB910900]
- Shandong Provincial Natural Science Foundation [2010GSF10218, JQ201007]
- Graduate Independent Innovation Foundation of Shandong University [YZC10040]
Salinomycin is perhaps the first promising compound that was discovered through high throughput screening in cancer stem cells. This novel agent can selectively eliminate breast and other cancer stem cells, though the mechanism of action remains unclear. In this study, we found that salinomycin induced autophagy in human non-small cell lung cancer (NSCLC) cells. Furthermore, we demonstrated that salinomycin stimulated endoplasmic reticulum stress and mediated autophagy via the ATF4-DDIT3/CHOP-TRIB3-AKT1-MTOR axis. Moreover, we found that the autophagy induced by salinomycin played a prosurvival role in human NSCLC cells and attenuated the apoptotic cascade. We also showed that salinomycin triggered more apoptosis and less autophagy in A549 cells in which CDH1 expression was inhibited, suggesting that the inhibition of autophagy might represent a promising strategy to target cancer stem cells. In conclusion, these findings provide evidence that combination treatment with salinomycin and pharmacological autophagy inhibitors will be an effective therapeutic strategy for eliminating cancer cells as well as cancer stem cells.
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