Riha Randal, Gupta-Saraf Pooja, Bhanja Payel, Badkul Samyak, Saha Subhrajit
Department of Radiation Oncology, University of Kansas Medical Center.
Department of Cancer Biology, University of Kansas Medical Center.
Oncomedicine. 2017;2:156-167. doi: 10.7150/oncm.22477. Epub 2017 Sep 27.
The unfolded protein response (UPR) is an established and well-studied cellular response to the stress and serves to relieve the stress and reinstate cellular homeostasis. It occurs in the endoplasmic reticulum (ER), responsible of properly folding and processing of secretory and transmembrane proteins. It is extremely sensitive to alteration in homeostasis caused by various internal or external stressors which leads to accumulation of misfolded or unfolded proteins in the ER lumen. The UPR works by restoring protein homeostasis in the ER, either through the boosting of protein-folding and degradation capability or by assuaging the demands for such effects, and can cause the activation of cell death if unable to do so. Cancer cells have adapted to gain advantage from the UPR and keeping the cell away from apoptosis and promoting survival, including survival of the cancer stem cells and evading the immune system. Several components of the UPR are overexpressed in a malignant cell and are responsible for resistance from various chemotherapy options and radiotherapy, which are also responsible for causing ER stress and activating the UPR. In this review, we discuss the various ways in which UPR can aid different cancers to survive and evade therapy and highlight recent research, which exploits the UPR to confer sensitivity to these cancer cells against various drugs and radiation.
未折叠蛋白反应（UPR）是一种已确立且经过充分研究的细胞对应激的反应，其作用是缓解应激并恢复细胞内稳态。它发生在内质网（ER）中，内质网负责分泌蛋白和跨膜蛋白的正确折叠和加工。它对各种内部或外部应激源引起的内稳态改变极为敏感，这些应激源会导致内质网腔中错误折叠或未折叠蛋白的积累。UPR通过增强蛋白折叠和降解能力或减轻对这种效应的需求来恢复内质网中的蛋白稳态，如果无法做到这一点，就会导致细胞死亡激活。癌细胞已经适应了从UPR中获得优势，使细胞远离凋亡并促进存活，包括癌症干细胞的存活和逃避免疫系统。UPR的几个组成部分在恶性细胞中过表达，并导致对各种化疗方案和放疗产生抗性，而这些治疗也会引起内质网应激并激活UPR。在本综述中，我们讨论了UPR帮助不同癌症存活和逃避免疫治疗的各种方式，并强调了最近的研究，即利用UPR使这些癌细胞对各种药物和辐射敏感。
