Randal Riha, Pooja Gupta-Saraf, Payel Bhanja, Samyak Badkul, Subhrajit Saha
{"title":"Stressed Out - Therapeutic Implications of ER Stress Related Cancer Research.","authors":"Randal Riha, Pooja Gupta-Saraf, Payel Bhanja, Samyak Badkul, Subhrajit Saha","doi":"10.7150/oncm.22477","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":91781,"journal":{"name":"Oncomedicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.7150/oncm.22477","citationCount":"28","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncomedicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.7150/oncm.22477","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2017/9/27 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 28
Abstract
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(unfolded protein response, UPR)是细胞对应激的反应,具有缓解应激和恢复细胞稳态的作用。它发生在内质网(ER),负责适当折叠和加工分泌和跨膜蛋白。内质网对各种内外应激源引起的内稳态改变极为敏感,从而导致内质网管腔内错误折叠或未折叠蛋白质的积累。UPR的工作原理是通过增强蛋白质折叠和降解能力或减轻对这种作用的需求来恢复内质网中的蛋白质稳态,如果不能这样做,则可能导致细胞死亡的激活。癌细胞已经适应了从普遍定期审议中获得优势,防止细胞凋亡,促进生存,包括癌症干细胞的生存和逃避免疫系统。UPR的几个组成部分在恶性细胞中过度表达,并负责对各种化疗方案和放疗的耐药性,这也负责引起内质网应激和激活UPR。在这篇综述中,我们讨论了UPR可以帮助不同癌症生存和逃避治疗的各种方式,并重点介绍了最近的研究,这些研究利用UPR赋予这些癌细胞对各种药物和辐射的敏感性。