内质网应激与癌症：未折叠蛋白反应能否成为癌症治疗的可靶向目标？
Endoplasmic Reticulum Stress and Cancer: Could Unfolded Protein Response Be a Druggable Target for Cancer Therapy?
机构信息
DiSIT-Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy.
出版信息
Int J Mol Sci. 2023 Jan 13;24(2):1566. doi: 10.3390/ijms24021566.
Abstract
Unfolded protein response (UPR) is an adaptive response which is used for re-establishing protein homeostasis, and it is triggered by endoplasmic reticulum (ER) stress. Specific ER proteins mediate UPR activation, after dissociation from chaperone Glucose-Regulated Protein 78 (GRP78). UPR can decrease ER stress, producing an ER adaptive response, block UPR if ER homeostasis is restored, or regulate apoptosis. Some tumour types are linked to ER protein folding machinery disturbance, highlighting how UPR plays a pivotal role in cancer cells to keep malignancy and drug resistance. In this review, we focus on some molecules that have been revealed to target ER stress demonstrating as UPR could be a new target in cancer treatment.
摘要
未折叠蛋白反应（UPR）是一种适应性反应，用于重新建立蛋白质的平衡，它是由内质网（ER）应激引发的。特定的 ER 蛋白在与伴侣葡萄糖调节蛋白 78（GRP78）分离后，介导 UPR 的激活。UPR 可以减少 ER 应激，产生 ER 的适应性反应，如果 ER 稳态得到恢复，则阻断 UPR，或者调节细胞凋亡。一些肿瘤类型与 ER 蛋白折叠机制的紊乱有关，这突出了 UPR 在维持癌细胞的恶性和耐药性方面所起的关键作用。在这篇综述中，我们重点介绍了一些已经被揭示靶向 ER 应激的分子，表明 UPR 可能是癌症治疗的一个新靶点。
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