信号转导和转录激活因子在癌症炎症与免疫中的作用：信号转导和转录激活因子3起主导作用
STATs in cancer inflammation and immunity: a leading role for STAT3.
作者信息
Yu Hua, Pardoll Drew, Jove Richard
机构信息
Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.
出版信息
Nat Rev Cancer. 2009 Nov;9(11):798-809. doi: 10.1038/nrc2734.
Abstract
Commensurate with their roles in regulating cytokine-dependent inflammation and immunity, signal transducer and activator of transcription (STAT) proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer. Persistently activated STAT3 and, to some extent, STAT5 increase tumour cell proliferation, survival and invasion while suppressing anti-tumour immunity. The persistent activation of STAT3 also mediates tumour-promoting inflammation. STAT3 has this dual role in tumour inflammation and immunity by promoting pro-oncogenic inflammatory pathways, including nuclear factor-kappaB (NF-kappaB) and interleukin-6 (IL-6)-GP130-Janus kinase (JAK) pathways, and by opposing STAT1- and NF-kappaB-mediated T helper 1 anti-tumour immune responses. Consequently, STAT3 is a promising target to redirect inflammation for cancer therapy.
摘要
信号转导和转录激活因子（STAT）蛋白在调节细胞因子依赖性炎症和免疫中发挥着相应作用，在决定肿瘤微环境中的免疫反应是促进还是抑制癌症方面起着核心作用。持续激活的STAT3以及在一定程度上的STAT5会增加肿瘤细胞的增殖、存活和侵袭，同时抑制抗肿瘤免疫。STAT3的持续激活还介导促肿瘤炎症。STAT3通过促进包括核因子-κB（NF-κB）和白细胞介素-6（IL-6）-糖蛋白130- Janus激酶（JAK）途径在内的促癌炎症途径，并通过对抗STAT1和NF-κB介导的辅助性T细胞1抗肿瘤免疫反应，在肿瘤炎症和免疫中具有这种双重作用。因此，STAT3是将炎症重定向用于癌症治疗的一个有前景的靶点。
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