Zhou Jing-Feng, Zhou Qin, Chen Chun, Pan Jing-Xuan
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China.
Division of Hematology/Oncology, Department of Pediatrics, the Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2021 Jan;52(1):11-15. doi: 10.12182/20210160503.
Metastasis is a multistep and low-efficiency biological process driven by acquisition of genetic and/or epigenetic alterations within tumor cells. These evolutionary alterations enable tumor cells to thrive in the inhospitable microenvironment they encounter in the process of metastasis and eventually lead to macroscopic metastases in distant organs. The unfolded protein response (UPR) induced by endoplasmic reticulum (ER) stress is one of the most important mechanisms regulating cellular adaptation to an adverse microenvironment. UPR is involved in all stages of metastasis, playing an important role in tumor cell growth, survival, and differentiation and the process of maintaining protein hemostasis. Sustained activation of ER stress sensors endows tumor cells with better epithelial-mesenchymal transition (EMT), survival, immune escape, angiogenesis, cellular adhesion, dormancy-to reactivation capacity in the process of metastasis. Here, we discussed the role of UPR in regulating the above-mentioned abilities of tumor cells during metastasis, providing a reference for development of new targets for the treatment of tumor metastasis.UPR in regulating the above-mentioned characteristics and mechanisms of tumor cells during metastasis, providing a reference for development of new targets for the treatment of tumor metastasis.
转移是一个多步骤且低效的生物学过程,由肿瘤细胞内遗传和/或表观遗传改变所驱动。这些进化改变使肿瘤细胞能够在转移过程中遇到的恶劣微环境中存活,并最终导致远处器官出现宏观转移。内质网(ER)应激诱导的未折叠蛋白反应(UPR)是调节细胞适应不良微环境的最重要机制之一。UPR参与转移的各个阶段,在肿瘤细胞的生长、存活、分化以及维持蛋白质稳态过程中发挥重要作用。ER应激传感器的持续激活赋予肿瘤细胞在转移过程中更好的上皮-间质转化(EMT)、存活、免疫逃逸、血管生成、细胞黏附、休眠-再激活能力。在此,我们讨论了UPR在转移过程中调节肿瘤细胞上述能力的作用,为开发治疗肿瘤转移的新靶点提供参考。UPR在转移过程中调节肿瘤细胞的上述特征和机制,为开发治疗肿瘤转移的新靶点提供参考。