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Reduced expression of the chromatin remodeling gene ARID1A enhances gastric cancer cell migration and invasion via downregulation of E-cadherin transcription  期刊论文  

  • 编号:
    7e389925-e001-43d0-b274-c7eba1f68905
  • 作者:
    Yan, HaiBo[1,2,3];Wang, XueFei[4];Zhang, Qian[1,2,3];Tang, ZhaoQing[4];Jiang, YingHua(姜英华)[3]Fan, HuiZhi[5];Sun, Yihong[4];Yang, PengYuan(杨芃原)[3,5]Liu, Feng(刘锋)[1,2,3]
  • 语种:
    English
  • 期刊:
    CARCINOGENESIS ISSN:0143-3334 2014 年 35 卷 4 期 (867 - 876) ; APR
  • 收录:
  • 摘要:

    The chromatin remodeling gene AT-rich interactive domain-containing protein 1A (ARID1A) encodes the protein BAF250a, a subunit of human SWI/SNF-related complexes. Recent studies have identified ARID1A as a tumor suppressor. Here, we show that ARID1A expression is reduced in gastric cancer (GC) tissues, which are significantly associated with local lymph node metastasis, tumor infiltration and poor patient prognosis. ARID1A silencing enforces the migration and invasion of GC cells, whereas ectopic expression of ARID1A inhibits migration. The adhesive protein E-cadherin is remarkably downregulated in response to ARID1A silencing, but it is upregulated by ARID1A overexpression. E-cadherin overexpression significantly inhibits GC cell migration and invasion, whereas CDH1 (coded E-cadherin) silencing promotes migration. Restored expression of CDH1 in ARID1A-silenced cell lines restores the inhibition of cell migration. Luciferase reporter assays and chromatin immunoprecipitation indicate that the ARID1A-associated SWI/SNF complex binds to the CDH1 promoter and modulates CDH1 transcription. ARID1A knockdown induces evident morphological changes of GC cells with increased expression of mesenchymal markers, indicating an epithelial-mesenchymal transition. ARID1A silencing does not alter the level of beta-catenin but induces a subcellular redistribution of beta-catenin from the plasma membrane to the cytoplasm and nucleus. Immunohistochemical studies demonstrate that reduced expression of E-cadherin is associated with local lymph node metastasis, tumor infiltration and poor clinical prognosis. ARID1A and E-cadherin expression show a strong correlation in 75.4% of the analyzed GC tissues. They are synergistically downregulated in 23.5% of analyzed GC tissues. In conclusion, ARID1A targets E-cadherin during the modulation of GC cell migration and invasion.

  • 推荐引用方式
    GB/T 7714:
    Yan Hai-Bo,Wang Xue-Fei,Zhang Qian, et al. Reduced expression of the chromatin remodeling gene ARID1A enhances gastric cancer cell migration and invasion via downregulation of E-cadherin transcription [J].CARCINOGENESIS,2014,35(4):867-876.
  • APA:
    Yan Hai-Bo,Wang Xue-Fei,Zhang Qian,Tang Zhao-Qing,&Liu Feng.(2014).Reduced expression of the chromatin remodeling gene ARID1A enhances gastric cancer cell migration and invasion via downregulation of E-cadherin transcription .CARCINOGENESIS,35(4):867-876.
  • MLA:
    Yan Hai-Bo, et al. "Reduced expression of the chromatin remodeling gene ARID1A enhances gastric cancer cell migration and invasion via downregulation of E-cadherin transcription" .CARCINOGENESIS 35,4(2014):867-876.
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