文章：

内质网蛋白折叠环境对癌症发展的影响

The impact of the endoplasmic reticulum protein-folding environment on cancer development

原文发布日期：2014-08-14

DOI: 10.1038/nrc3800

类型: Review Article

开放获取: 否

要点：

1. Defective protein folding in the endoplasmic reticulum (ER) and unfolded protein response (UPR) activation are documented in many human cancer types, which is attributed to both intrinsic and extrinsic factors.
2. UPR activation is a vital step for oncogenic transformation, as UPR signalling molecules interact with well-established oncogene and tumour suppressor gene networks to modulate their function during cancer development.
3. Conditions of low nutrient supply (for example, glucose or oxygen deprivation), as well as excess nutrients (fatty acids, cholesterol and glucose) induce ER stress and UPR activation. UPR induction promotes cancer cell survival through induction of autophagy and adaptation to the stressful microenvironment.
4. ER stress and UPR activation possibly promote cancer development and progression through modulating inflammatory responses.
5. The UPR is indispensable in cells in the tumour microenvironment to either promote or inhibit cancer progression.
6. Targeting the UPR, through single or combination therapy, provides a promising therapeutic approach for many different cancers.

要点翻译：

1. 内质网中蛋白质错误折叠与未折叠蛋白反应的激活在多种人类癌症中均有记载，这归因于内在和外在双重因素。
2. 未折叠蛋白反应是致癌转化过程中的关键步骤，因为其信号分子与公认的致癌基因和抑癌基因网络相互作用，在癌症发展中调控其功能。
3. 营养供应不足（如葡萄糖或氧气缺乏）以及营养过剩（脂肪酸、胆固醇和葡萄糖）均可诱导内质网应激并激活未折叠蛋白反应。该反应的激活通过诱导自噬及促进癌细胞适应应激微环境来维持其存活。
4. 内质网应激与未折叠蛋白反应可能通过调节炎症反应促进癌症的发生发展。
5. 在肿瘤微环境中，未折叠蛋白反应对细胞促进或抑制癌症进展具有不可或缺的作用。
6. 通过单一或联合疗法靶向未折叠蛋白反应，为多种癌症提供了前景广阔的治疗策略。

英文摘要：

The endoplasmic reticulum (ER) is an essential organelle in eukaryotic cells for the storage and regulated release of calcium and as the entrance to the secretory pathway. Protein misfolding in the ER causes accumulation of misfolded proteins (ER stress) and activation of the unfolded protein response (UPR), which has evolved to maintain a productive ER protein-folding environment. Both ER stress and UPR activation are documented in many different human cancers. In this Review, we summarize the impact of ER stress and UPR activation on every aspect of cancer and discuss outstanding questions for which answers will pave the way for therapeutics.

摘要翻译： 

内质网（ER）是真核细胞中储存和调控钙离子释放的重要细胞器，也是分泌途径的入口。内质网中蛋白质的错误折叠会导致错误折叠蛋白的积聚（即内质网应激），并激活未折叠蛋白反应（UPR），该反应已进化出维持内质网高效蛋白质折叠环境的功能。内质网应激和UPR激活已在多种人类癌症中被证实。在本综述中，我们总结了内质网应激和UPR激活对癌症各方面的影响，并探讨了亟待解决的问题，其答案将为治疗铺平道路。

原文链接：

The impact of the endoplasmic reticulum protein-folding environment on cancer development