Unfolded protein response in cancer: the physician's perspective.

Unfolded protein response in cancer: the physician's perspective.
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DOI:
10.1186/1756-8722-4-8
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发表时间:
2011-02-23
影响因子:
28.5
通讯作者:
Li Z
Li Z
中科院分区:
医学1区
文献类型:
--
作者:
Li X;Zhang K;Li Z

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未折叠蛋白反应(UPR)是响应于未折叠或错误折叠的蛋白质在内质网(ER)腔中的积累的细胞内应激信号传导事件的级联。癌细胞经常暴露于缺氧、营养饥饿、氧化应激和其他代谢失调,导致ER应激和UPR活化。根据ER应激的持续时间和程度,UPR可以通过激活适应性和抗凋亡途径提供生存信号,或通过诱导细胞死亡程序提供死亡信号。因此,持续诱导或抑制UPR β可能对癌症具有有益的治疗作用。本文就UPR的基本机制及其在肿瘤生物学中的重要性进行综述。我们还更新了目前在临床试验中的UPR靶向癌症治疗方法。
The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic effects against cancer. In this review, we discuss the basic mechanisms of UPR and highlight the importance of UPR in cancer biology. We also update the UPR-targeted cancer therapeutics currently in clinical trials.
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