The switch from ER stress-induced apoptosis to autophagy via ROS-mediated JNK/p62 signals: A survival mechanism in methotrexate-resistant choriocarcinoma cells
The switch from ER stress-induced apoptosis to autophagy via ROS-mediated JNK/p62 signals: A survival mechanism in methotrexate-resistant choriocarcinoma cells
复制标题
通过 ROS 介导的 JNK/p62 信号从 ER 应激诱导的细胞凋亡转变为自噬：甲氨蝶呤耐药绒毛膜癌细胞的生存机制
DOI：
10.1016/j.yexcr.2015.04.010
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发表时间：
2015-06-10
影响因子：
3.7
通讯作者：
Xiang, Yang
中科院分区：
文献类型：
--
作者：
Shen, Yun;Yang, Junjun;Xiang, Yang
Background: Human choriocarcinoma, a highly curable solid tumour, is exceptionally sensitive to methotrexate-based chemotherapy at the metastatic stage. The present study aimed to investigate the molecular basis for this resistance to methotrexate therapy occurs in some cases, and these patients subsequently die from progressive and advanced disease.Methods: The autophagy and apoptotic activity regulated by PERK/ATF4 axis in methotrexate-resistant JEG-3 and parental cells were evaluated with western blotting and chromatin immunoprecipitation (ChIP). The regulatory relationships among the reactive oxygen species (ROS), JNK/p62 axis, PERK/ATF4-mediated apoptosis and autophagy were assessed with western blotting, RT-PCR, fluorescence-activated cell sorting as well as ChIP.Results: The decreased apoptosis in methotrexate-resistant JEG-3 cells was observed with an up-regulation of protective autophagy, suggesting a switch from apoptosis to autophagy, which was regulated via the PERK/ATF4 pathway under condition of endoplasmic reticulum (ER) stress. Further experiments demonstrated that this cell death switch was regulated by ROS-mediated JNK/p62 pathway and subsequently lead to the resistance of choriocarcinoma cells to methotrexate treatment.Conclusions: This study provides evidence to explain a survival mechanism of the switch from ER stress-induced apoptosis to autophagy via ROS-mediated JNK/p62 signals in methotrexate-resistant choriocarcinoma cells and may implicate the chemotherapy of methotrexate resistance in choriocarcinoma. (C) 2015 Elsevier Inc. All rights reserved.
