摘要
信号传导与转录活化因子3(signal transducers and activators of transcription,STAT3)信号通路参与细胞因子及生长因子介导的信号转导。STAT3的持续激活与多种肿瘤的发生发展密切相关。STAT3可影响以DNA及组蛋白修饰为主的表观遗传修饰的异常调控:一方面,表观遗传修饰相关酶类可受到STAT3的转录调节;另一方面,STAT3可与其形成功能复合物调控其下游基因表达。STAT3的非磷酸化形式亦可直接影响局部表观遗传修饰。STAT3通过与表观遗传修饰系统的相互作用,可影响局部染色质构象,参与下游关键基因的转录调节,也可维持自身信号通路在肿瘤中的持续活化。阐明STAT3信号通路与表观遗传修饰异常的调控关系,将有助于进一步明确相关肿瘤的发病机制,为临床治疗提供新途径。
Signal transducers and activators of transcription(STAT3)signaling is a key pathway involved in cytokine and growth factor mediated signal transduction.Its persistent activation is closely related to the development of various tumors.STAT3 pathway has been reported to influence the dysregulation of epigenetic modifications mainly including the DNA and histone modifications:on the one hand,epigenetic modification enzymes can be transcriptionally regulated by STAT3;on the other,STAT3 directly interacts with epigenetic modification enzymes to form a functional complex to regulate downstream gene expression.Unphosphorylated STAT3 can also directly affect local epigenetic modifications.STAT3 cooperates with epigenetic modification systems to affect local chromatin conformation,leading to transcriptional regulation of key downstream genes,and maintain persistent activation of its signaling pathway in tumors.Elucidation of the regulatory networks between STAT3 signaling pathway and epigenetic modifications will shed light on the understanding of related tumorigenesis mechanisms,and offer novel clues for cancer therapy.
作者
代楚君
王筝扬
沈静
DAI Chu-Jun;WANG Zheng-Yang;SHEN Jing(Department of Pathology and Pathophysiology,Zhejiang University School of Medicine,Hangzhou 310058,China;Department of Pulmonology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2019年第9期939-944,共6页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金(No.81772919)
浙江省医药卫生科技资助项目(No.2018KY119)
浙江省自然科学基金(No.LY18H160024)资助~~
关键词
信号传导与转录活化因子3
肿瘤
表观遗传修饰
signal transducers and activators of transcription(STAT3)
tumor
epigenetic modification
作者简介
通讯作者:沈静,Tel:0571-88208210,E-mail:shenjingwzy@zju.edu.cn
