STAT3对EMT的调节和对循环肿瘤细胞与肿瘤侵袭及转移的影响  

Roles of STAT3 in Regulation of EMT-mediated Phenotypic Plasticity and Its Effects on Circulating Tumor Cells and Tumor Invasion and Metastases

作　　者：姜雨[1,2] 丁怡[1] 李文卿[1,2] 路中[1,2] 张建[3] 杨小毅[4] 王丽华[1,2] 

机构地区：[1]潍坊医学院分子肿瘤学研究室,潍坊261053 [2]潍坊医学院附属医院,潍坊261053 [3]山东大学药学院,济南250012 [4]泰山医学院,泰安271018

出　　处：《生物化学与生物物理进展》2016年第7期644-651,共8页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(81472489);山东省科技发展计划(2014GGB14403)资助项目~~

摘　　要：信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)参与了机体许多生理和病理过程.近年来发现,STAT3尽管不是上皮-间充质表型转换(epithelial-mesenchymal transition,EMT)的管家转录因子,但是却参与EMT相关基因的表达,影响肿瘤细胞的表型可塑性,从而参与循环肿瘤细胞(circulating tumor cells)的形成及表型特征的变化,与肿瘤的转移、侵袭密切相关.一方面上游信号可以激活STAT3,磷酸化STAT3可以入核绑定特定EMT管家转录因子(Twist、Snail、Slug等)启动子上的特定片段,从而调节肿瘤细胞中的EMT程序启动和析解.另一方面,当STAT3作为一种分子适配器(adaptor)而非转录因子作用时,又可抑制EMT.因此,对STAT3与EMT相互作用及其对循环肿瘤细胞影响的认识,将有助于开拓肿瘤转移治疗的新思路.The signal transduction and transcriptional activation factor 3（STAT3） plays important roles in many physiological and pathological processes.Although STAT3 is not a classic member of master transcription factors of epithelial-mesenchymal transition（EMT）,STAT3 has recently also been documented to be a mediator of tumor cell phenotypic plasticity,in turn affecting formation and phonotypic characteristic of circulating tumor cells,which are associated with invasion and metastases of tumor cells.Activation of STAT3 can translocate into the nucleus and bind to specific promoter sequences of various EMT master transcription factors such as Twist,Snail,and Slug,resulting in the initiation and resolution of EMT programs in malignant cells,which promotes invasion and metastases of developing tumors.On the other hand,inactivated STAT3 may also function as a molecular adaptor to inhibit EMT programs.Therefore,understanding of the interaction between STAT3 and EMT and its effects on circulating tumor cells may provide new approaches for treatment of metastatic carcinomas.

关 键 词：STAT3 EMT 恶性肿瘤 信号通路 循环肿瘤细胞 

分 类 号：R73[医药卫生—肿瘤]