Targeting ER stress induced apoptosis and inflammation in cancer
Targeting ER stress induced apoptosis and inflammation in cancer
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DOI：
10.1016/j.canlet.2010.07.016
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发表时间：
2013-05-28
期刊：
影响因子：
9.7
通讯作者：
Agostinis, Patrizia
中科院分区：
文献类型：
--
作者：
Verfaillie, Tom;Garg, Abhishek D.;Agostinis, Patrizia
内质网(ER)折叠能力的障碍，由各种内源性和外源性的侮辱引起，促使一种称为内质网应激的细胞应激状态。内质网应激最初是通过激活被称为未折叠蛋白反应(UPR)的整合的细胞内信号转导通路来重建内质网稳态的。然而，当内质网应激过强或过长时，UPR的促生存功能转变为一种毒性信号，主要由线粒体凋亡来执行。此外，越来越多的证据表明，内质网应激通路参与了肿瘤微环境内和周围各种经典的炎症过程的激活。事实上，已发现某些传统或实验性抗癌方式所激发的内质网应激通路通过增强濒临死亡的癌细胞的免疫原性来促进抗肿瘤免疫。因此，内质网起着重要的传感细胞器的作用，能够协调压力途径，在维持癌细胞的细胞内和细胞外环境之间的串扰方面起着至关重要的作用。在这篇综述中，我们讨论了内质网应激、细胞命运决定和免疫调节之间的新出现的联系，以及在抗癌治疗中靶向这一多方面的信号通路的潜在治疗益处。(C)2010爱思唯尔爱尔兰有限公司。保留所有权利。
Disturbance in the folding capacity of the endoplasmic reticulum (ER), caused by a variety of endogenous and exogenous insults, prompts a cellular stress condition known as ER stress. ER stress is initially shaped to re-establish ER homeostasis through the activation of an integrated intracellular signal transduction pathway termed as unfolded protein response (UPR). However, when ER stress is too severe or prolonged, the pro-survival function of the UPR turns into a toxic signal, which is predominantly executed by mitochondrial apoptosis. Moreover, accumulating evidence implicates ER stress pathways in the activation of various 'classical' inflammatory processes in and around the tumour microenvironment In fact, ER stress pathways evoked by certain conventional or experimental anticancer modalities have been found to promote anti-tumour immunity by enhancing immunogenicity of dying cancer cells. Thus, the ER functions as an essential sensing organelle capable of coordinating stress pathways crucially involved in maintaining the crosstalk between the cancer cell's intracellular and extracellular environment. In this review we discuss the emerging link between ER stress, cell fate decisions and immunomodulation and the potential therapeutic benefit of targeting this multifaceted signaling pathway in anticancer therapy. (C) 2010 Elsevier Ireland Ltd. All rights reserved.