Inserm U1242 'Chemistry, Oncogenesis, Stress & Signaling', Université de Rennes, Rennes, France.
Centre de Lutte Contre le Cancer Eugene Marquis, Rennes, France.
FEBS J. 2019 Jan;286(2):279-296. doi: 10.1111/febs.14359. Epub 2017 Dec 29.
The unfolded protein response (UPR) is a conserved adaptive pathway that helps cells cope with the protein misfolding burden within the endoplasmic reticulum (ER). Imbalance between protein folding demand and capacity in the ER leads to a situation called ER stress that is often observed in highly proliferative and secretory tumor cells. As such, activation of the UPR signaling has emerged as a key adaptive mechanism promoting cancer progression. It is becoming widely acknowledged that, in addition to its intrinsic effect on tumor biology, the UPR can also regulate tumor microenvironment. In this review, we discuss how the UPR coordinates the crosstalk between tumor and stromal cells, such as endothelial cells, normal parenchymal cells, and immune cells. In addition, we further describe the involvement of ER stress signaling in the response to current treatments as well as its impact on antitumor immunity mainly driven by immunogenic cell death. Finally, in this context, we discuss the relevance of targeting ER stress/UPR signaling as a potential anticancer approach.
未折叠蛋白反应（UPR）是一种保守的适应性途径，有助于细胞应对内质网（ER）内的蛋白质错误折叠负担。ER 中蛋白质折叠需求和能力之间的失衡导致 ER 应激，这种情况在高度增殖和分泌的肿瘤细胞中经常观察到。因此，UPR 信号的激活已成为促进癌症进展的关键适应机制。人们越来越认识到，除了对肿瘤生物学的内在影响外，UPR 还可以调节肿瘤微环境。在这篇综述中，我们讨论了 UPR 如何协调肿瘤细胞与基质细胞（如内皮细胞、正常实质细胞和免疫细胞）之间的串扰。此外，我们还进一步描述了 ER 应激信号在对当前治疗的反应中的参与及其对主要由免疫原性细胞死亡驱动的抗肿瘤免疫的影响。最后，在这种情况下，我们讨论了作为一种潜在抗癌方法靶向 ER 应激/UPR 信号的相关性。
