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首页> 外文期刊>Cell cycle >Wilms' tumor 1 (WT1) promotes ovarian cancer progression by regulating E-cadherin and ERK1/2 signaling
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Wilms' tumor 1 (WT1) promotes ovarian cancer progression by regulating E-cadherin and ERK1/2 signaling

机译：Wilms的肿瘤1（wt1）通过调节E-cadherin和ERK1 / 2信号传导来促进卵巢癌进展

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摘要

Wilms' tumor 1 (WT1) is reported to play an important role in tumor invasion and metastasis, two hallmarks of ovarian cancer (OC) that influence treatment efficacy and prognosis. However, the specific roles and underlying mechanisms ofWT1in OC have not been fully understood. Here, we investigated the potential function and signaling pathways ofWT1in OC cells. We showed that WT1 was significantly upregulated in human OC tissues and closely associated with OC type, grade and FIGO stage. In cultured cells and xenograft mouse models,WT1depletion significantly inhibited cell migration and invasion, reversed epithelial-mesenchymal transition (EMT), and prevented metastasis of OC cells. We further demonstrated thatWT1inhibited E-cadherin expression via targetingE-cadheringene promoter by chromatin immunoprecipitation and luciferase reporter assay. Moreover, ERK1/2 activation was suppressed uponWT1silencing. Inhibiting ERK1/2 phosphorylation increased E-cadherin expression and suppressed WT1-induced OC cell migration and invasion. Taken together, our study revealsWT1exerts a tumor-promoting role in OC, enhancing EMT through negative modulation of E-cadherin expression via ERK1/2 signaling.WT1may represent a novel therapeutic target that may improve the prognosis of OC.
机译：据报道，Wilms’s tumor 1（WT1）在肿瘤侵袭和转移中发挥重要作用，这是卵巢癌（OC）的两个特征，影响治疗效果和预后。然而，WT1在OC中的具体作用和潜在机制尚未完全了解。在这里，我们研究了WT1OC细胞的潜在功能和信号通路。我们发现WT1在人类OC组织中显著上调，并与OC类型、分级和FIGO分期密切相关。在培养细胞和异种移植小鼠模型中，WT1置换显著抑制细胞迁移和侵袭，逆转上皮-间充质转化（EMT），并防止OC细胞的转移。我们通过染色质免疫沉淀和荧光素酶报告分析进一步证明WT1通过靶向钙粘蛋白基因启动子抑制E-钙粘蛋白表达。此外，ERK1/2的激活被抑制。抑制ERK1/2磷酸化可增加E-钙粘蛋白的表达，并抑制WT1诱导的OC细胞迁移和侵袭。综上所述，我们的研究揭示了卵巢癌中的肿瘤促进作用，通过ERK1/2信号传导负性调节E-钙粘蛋白表达，增强EMT。WT1可能是改善OC预后的一个新的治疗靶点。

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  • 来源
    《Cell cycle》 |2020年第20期|共14页
  • 作者

    Han Yun; Song Chao; Zhang Tingting; Zhou Qianqian; Zhang Xiaoqian; Wang Jing; Xu Boqun; Zhang Xuesen; Liu Xiaoqiu; Ying Xiaoyan;

  • 作者单位

    Nanjing Med Univ Affiliated Hosp 2 Dept Obstet &

    Gynecol Nanjing Jiangsu Peoples R China;

    First Peoples Hosp Nantong City Nantong Jiangsu Peoples R China;

    Nanjing Drum Tower Hosp Grp Suqian Peoples Hosp Dept Obstet &

    Gynecol Suqian Jiangsu Peoples R;

    First Peoples Hosp Nantong City Nantong Jiangsu Peoples R China;

    First Peoples Hosp Nantong City Nantong Jiangsu Peoples R China;

    Nanjing Med Univ Affiliated Hosp 2 Dept Obstet &

    Gynecol Nanjing Jiangsu Peoples R China;

    Nanjing Med Univ Affiliated Hosp 2 Dept Obstet &

    Gynecol Nanjing Jiangsu Peoples R China;

    First Peoples Hosp Nantong City Nantong Jiangsu Peoples R China;

    Nanjing Med Univ Dept Microbiol Key Lab Pathogen Biol Jiangsu Prov Nanjing Peoples R China;

    Nanjing Med Univ Affiliated Hosp 2 Dept Obstet &

    Gynecol Nanjing Jiangsu Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    Ovarian cancer; WT1; migration and invasion; EMT; ERK1; 2 signaling;

    机译：卵巢癌;WT1;迁移和入侵;EMT;ERK1;2信号传导;

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