肌动蛋白结合蛋白Anillin通过靶向细胞核中的c-Myc介导上皮–间质转化并促进胃癌进展  

Anillin Mediates EMT by Targeting c-Myc in the Nucleus and Potentiates Gastric Carcinoma Progression

作　　者：符明诗 史珂 刘东洋 陈风[2] FU Mingshi;SHI Ke;LIU Dongyang;CHEN Feng(College of Fisheries and Life Science,Shanghai Ocean University,Shanghai 201306,China;Division of General Surgery,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Shanghai 200233,China)

机构地区：[1]上海海洋大学水产与生命科学学院,上海201306 [2]上海第六人民医院普外科,上海200233

出　　处：《中国细胞生物学学报》2022年第6期1020-1030,共11页Chinese Journal of Cell Biology

基　　金：上海医药卫生大学国家培养计划项目(批准号:SFP-18-20-14-005);上海市浦东新区科技发展基金(批准号:PKJ2016-Y54)资助的课题。

摘　　要：肌动蛋白结合蛋白(ANLN)在细胞增殖和迁移中起重要作用,特别是在胞质分裂中。虽然已有研究结果表明癌症的发生发展与ANLN有关,但其影响胃癌(GC)发生发展的潜在调控作用和分子机制仍不清楚。在此,先采用伤口愈合实验、Trans-well实验和基质(Matrigel) Trans-well实验检测ANLN表达情况对体外胃癌细胞迁移和侵袭能力的影响。然后,采用免疫印迹实验来评估上皮–间充质转化(EMT)相关蛋白和Smad蛋白的表达。此外,还采用共定位免疫荧光法、免疫共沉淀法(Co-IP)和Western blot探索ANLN参与胃癌转移的分子机制。在此研究中,沉默ANLN减弱了胃癌细胞的迁移和侵袭能力。在机制上,ANLN可以与细胞核中的c-Myc 相互作用,随后c-Myc 发生磷酸化,诱导Snail和Slug转录因子的表达,促进EMT,但不激活Smads蛋白。总的来说,该文的数据揭示了一个潜在的分子机制,即ANLN通过分别介导Smads信号通路和c-Myc 蛋白进而靶向调控下游转录因子(Snail和Slug)触发EMT进程。ANLN (Anillin),an actin-binding protein,reportedly plays a vital role in cell proliferation and migration,particularly in cytokinesis.Although there have been findings pointing to a contribution of ANLN to the development of cancer,the potential regulatory roles and molecular mechanisms by which ANLN affects the development and progression of GC (gastric carcinoma) remain obscure.Herein,applying wound healing assay,Trans-well migration and Matrigel Trans-well assays to detect the effect of ANLN expression on migration and invasion ability of GC cells in vitro.Then,performing Western blot to evaluate EMT (epithelial-mesenchymal transition) associated proteins and Smad proteins.Moreover,performing immunofluorescence assay,Co-IP (co-immunoprecipitation) assay and Western blot to explore molecular mechanisms by which ANLN is involved in GC metastasis.In this study,ANLN silencing attenuated GC cell migration and invasion.Mechanistically,ANLN could interact with c-Myc in the nucleus and subsequently phosphorylate c-Myc to induce the expression of Snail and Slug transcription factors,to promote EMT but does not activate Smad proteins.Collectively,the data reveal a potential molecular mechanism in which ANLN mediates Smads signaling pathway and c-Myc protein respectively,which target downstream transcription factors (Snail and Slug) to trigger EMT.

关 键 词：肌动蛋白结合蛋白(ANLN) 胃癌(GC) C-MYC 上皮–间质转化(EMT) Smads 

分 类 号：R735.2[医药卫生—肿瘤]