文章：

肿瘤及其微环境中的内质网应激信号

Endoplasmic reticulum stress signals in the tumour and its microenvironment

原文发布日期：2020-11-19

DOI: 10.1038/s41568-020-00312-2

类型: Review Article

开放获取: 否

英文摘要：

Protein handling, modification and folding in the endoplasmic reticulum (ER) are tightly regulated processes that determine cell function, fate and survival. In several tumour types, diverse oncogenic, transcriptional and metabolic abnormalities cooperate to generate hostile microenvironments that disrupt ER homeostasis in malignant and stromal cells, as well as infiltrating leukocytes. These changes provoke a state of persistent ER stress that has been demonstrated to govern multiple pro-tumoural attributes in the cancer cell while dynamically reprogramming the function of innate and adaptive immune cells. Aberrant activation of ER stress sensors and their downstream signalling pathways have therefore emerged as key regulators of tumour growth and metastasis as well as response to chemotherapy, targeted therapies and immunotherapy. In this Review, we discuss the physiological inducers of ER stress in the tumour milieu, the interplay between oncogenic signalling and ER stress response pathways in the cancer cell and the profound immunomodulatory effects of sustained ER stress responses in tumours.

摘要翻译： 

内质网中的蛋白质处理、修饰与折叠是决定细胞功能、命运与存活的精密调控过程。在多种肿瘤类型中，不同的致癌性、转录及代谢异常共同作用，在恶性细胞、基质细胞及浸润白细胞中形成破坏内质网稳态的恶劣微环境。这些变化引发持续性内质网应激状态，该状态已被证实不仅能调控癌细胞的多种促肿瘤特性，还能动态重编程先天性与适应性免疫细胞的功能。因此，内质网应激传感器及其下游信号通路的异常激活，已成为肿瘤生长转移以及对化疗、靶向治疗和免疫治疗反应的关键调控机制。本文综述中，我们将探讨肿瘤微环境中内质网应激的生理诱导因子、癌细胞中致癌信号与内质网应激应答途径的相互作用，以及持续性内质网应激反应在肿瘤中产生的深远免疫调节效应。

原文链接：

Endoplasmic reticulum stress signals in the tumour and its microenvironment