Tameire Feven, Verginadis Ioannis I, Koumenis Constantinos
Department of Radiation Oncology, Perelman University School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Program in Cell and Molecular Biology, Perelman University School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Radiation Oncology, Perelman University School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Semin Cancer Biol. 2015 Aug;33:3-15. doi: 10.1016/j.semcancer.2015.04.002. Epub 2015 Apr 25.
A variety of cell intrinsic or extrinsic stresses evoke perturbations in the folding environment of the endoplasmic reticulum (ER), collectively known as ER stress. Adaptation to stress and re-establishment of ER homeostasis is achieved by activation of an integrated signal transduction pathway called the unfolded protein response (UPR). Both ER stress and UPR activation have been implicated in a variety of human cancers. Although at early stages or physiological conditions of ER stress, the UPR generally promotes survival, when the stress becomes more stringent or prolonged, its role can switch to a pro-cell death one. Here, we discuss historical and recent evidence supporting an involvement of the UPR in malignancy, describe the main mechanisms by which tumor cells overcome ER stress to promote their survival, tumor progression and metastasis and discuss the current state of efforts to develop therapeutic approaches of targeting the UPR.
多种细胞内在或外在应激会引发内质网（ER）折叠环境的紊乱，统称为内质网应激。通过激活一种称为未折叠蛋白反应（UPR）的整合信号转导途径，可实现对应激的适应和内质网稳态的重建。内质网应激和UPR激活均与多种人类癌症有关。尽管在早期内质网应激阶段或生理条件下，UPR通常促进细胞存活，但当应激变得更加严重或持续时间延长时，其作用可能会转变为促进细胞死亡。在此，我们讨论支持UPR参与恶性肿瘤的历史和最新证据，描述肿瘤细胞克服内质网应激以促进其存活、肿瘤进展和转移的主要机制，并讨论开发靶向UPR治疗方法的当前进展情况。
