School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
School of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, 430023, China.
Cancer Lett. 2019 May 1;449:263-271. doi: 10.1016/j.canlet.2019.01.034. Epub 2019 Feb 15.
The endoplasmic reticulum (ER) is the primary organelle responsible for the synthesis, modification, folding and secretion of proteins, especially in specialized secretory cells. It also contributes to the maintenance of cellular functions, such as Ca storage, lipogenesis, gluconeogenesis, and organelle biogenesis. Cellular stress conditions, such as glucose deprivation, hypoxia and disturbance of Ca homeostasis, may increase the risk of protein misfolding and perturb proteostasis. This activates ER stress and triggers the unfolded protein response (UPR), leading to either the restoration of homeostasis or cell death. ER stress and UPR have been shown to play crucial roles in the pathogenesis, progression and treatment response of various cancers. In gastric cancer (GC), one of the most aggressive cancer types, critical functions of ER stress signaling have also started to emerge. Herein, we summarize the current knowledge linking ER stress and UPR to GC; we also discuss the possible nodes of therapeutic intervention and propose directions of future research.
内质网（ER）是负责蛋白质合成、修饰、折叠和分泌的主要细胞器，尤其是在专门的分泌细胞中。它还有助于维持细胞功能，如钙储存、脂肪生成、糖异生和细胞器发生。细胞应激条件，如葡萄糖剥夺、缺氧和钙稳态紊乱，可能会增加蛋白质错误折叠的风险并扰乱蛋白质稳态。这会激活内质网应激并触发未折叠蛋白反应（UPR），导致稳态的恢复或细胞死亡。内质网应激和 UPR 已被证明在各种癌症的发病机制、进展和治疗反应中发挥关键作用。在胃癌（GC）中，一种最具侵袭性的癌症类型，内质网应激信号的关键功能也开始显现。在此，我们总结了将内质网应激和 UPR 与 GC 联系起来的最新知识；我们还讨论了可能的治疗干预节点，并提出了未来研究的方向。
