未折叠蛋白反应
生物
XBP1型
癌细胞
细胞生物学
丙酮酸激酶
瓦博格效应
重编程
癌症研究
下调和上调
蜗牛
激酶
糖酵解
癌症
细胞
生物化学
内质网
新陈代谢
遗传学
生态学
核糖核酸
RNA剪接
基因
作者
Xike Mao,Chenxi Yu,Feng Yin,Wenjiao Xu,Yonghan Pan,Bowen Yang,Tao Huang,Siling Chen,Wenge Luo,Tianyu Su,Zhihao Wu
标识
DOI:10.1016/j.yexcr.2022.113376
摘要
Mounting evidence indicates that activation of unfolded protein response (UPR) and metabolic reprogramming contribute to cancer cell migration and invasion, but the molecular mechanism of pro-EMT program through a coordinated action of UPR with metabolism has not been defined. In this study, we utilized ER stress-inducing reagent, thapsigargin (TG), to induced pharmacologic ER stress in lung cancer cells. Here. We report that the branch of UPR, IRE1α-XBP1 pathway plays a pivotal role in reprogramming lung cancer cell metabolism. At the molecular level, the expression of pyruvate dehydrogenase kinase-1 (PDK-1) is directly induced by XBP1 as a consequence of UPR activation, thus facilitating aerobic glycolysis and lactate production. We also demonstrated that PDK1 serves as a downstream element of UPR activation in induction of Snail and EMT program. In addition, PDK1-induced Snail was dependent on the lactate production derived from metabolic reprogramming. Our findings reveal a critical role of lactate in pro-invasion events and establishes a direct connection between ER-stress and metabolic reprogramming in facilitating cancer cell progression.
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