Endoplasmic reticulum stress signals in the tumour and its microenvironment.

Endoplasmic reticulum stress signals in the tumour and its microenvironment.
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DOI:
10.1038/s41568-020-00312-2
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发表时间:
2021-03
期刊:
Nature reviews. Cancer
影响因子:
--
通讯作者:
Cubillos-Ruiz JR
Cubillos-Ruiz JR
中科院分区:
其他
文献类型:
--
作者:
Chen X;Cubillos-Ruiz JR

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内质网(ER)中的蛋白质处理、修饰和折叠是决定细胞功能、命运和存活的严格调控过程。在几种肿瘤类型中,不同的致癌、转录和代谢异常协同产生不利的微环境,破坏恶性和基质细胞以及浸润性白细胞中的ER稳态。这些变化引起了持续的ER应激状态,已被证明可以控制癌细胞中的多种促肿瘤属性,同时动态地重新编程先天性和适应性免疫细胞的功能。因此,ER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和转移以及对化疗、靶向治疗和免疫治疗的反应的关键调节剂。在这篇综述中,我们讨论了ER应激在肿瘤环境中的生理诱导剂,致癌信号传导和ER应激反应途径在癌细胞中的相互作用,以及持续的ER应激反应在肿瘤中的深刻的免疫调节作用。
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.
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