Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis

作     者：Zhenxing Gao Min Peng Liang Chen Xiaowen Yang Huan Li Run Shi Guiru Wu Lili Cai Qibin Song Chaoyang Li 

作者机构：State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences Wuhan 430071 China Department of Oncology Renmin Hospital of Wuhan University Wuhan 430060 China Department of the First Abdominal Surgery Jiangxi Tumor Hospital Nanchang 330029 China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2019年第34卷第2期

页      面：222-234页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 

基　　金：supported by the Strategic Priority Research Program A of the Chinese Academy of Sciences (XDA12010309) the National Natural Science Foundation of China (31670170 and 31270209) the National Key R&D program of China (2018YFA0507201) the National Basic Research Priorities Program of China (2013CB911102) from the Ministry of Science and Technology of China 

主　　题：Endoplasmic reticulum stress Brefeldin A (BFA) Prion protein (PrP)- Glycosylation Apoptosis 

摘      要：Unfolded protein response(UPR) is an adaptive reaction for cells to reduce endoplasmic reticulum(ER) stress. In many types of cancers, such as lung cancer and pancreatic cancer, cancer cells may harness ER stress to facilitate their survival and growth. Prion protein(PrP) is a glycosylated cell surface protein that has been shown to be up-regulated in many cancer cells. Since PrP is a protein prone to misfolding, ER stress can result in under-glycosylated PrP, which in turn may activate ER stress. To assess whether ER stress leads to the production of under-glycosylated PrP and whether underglycosylated PrP may contribute to ER stress thus leading to cancer cell apoptosis, we treated different cancer cells with brefeldin A(BFA), thapsigargin(Thps), and tunicamycin(TM). We found that although BFA, Thps, and TM treatment activated UPR, only ATF4 was consistently activated by these reagents, but not other branches of ER stress. However, the canonical PERK-eIF2α-ATF4 did not account for the observed activation of ATF4 in lung cancer cells. In addition, BFA,but neither Thps nor TM, significantly stimulated the expression of cytosolic PrP. Finally, we found that the levels of PrP contributed to anti-apoptosis activity of BFA-induced cancer cell death. Thus, the pathway of BFA-induced persistent ER stress may be targeted for lung and pancreatic cancer treatment.