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Cell Death Dis:PCDHGA9通过降低β-catenin转录活性抑制胃癌上皮-间质转化及转移潜能

2020-04-14 QQY MedSci原创

PCDHGA9通过介导Wnt/β-catenin信号通路和TGF-β通路抑制上皮-间质转化(EMT)过程, 还能够抑制癌细胞的侵袭及转移.

作为2018年全球癌症相关死亡的第二大诱因及第六大最常被诊断出的癌症,胃癌(GC)具有高死亡率及预后差等特点,其5年生存率不到30%,且胃癌的转移是提高其治疗效果的主要障碍。肿瘤转移是一个多步骤的、多分子参与的过程。彻底了解GC的转移机制对于开发新型的治疗策略具有重要意义。关键基因的调控对于肿瘤的侵袭及转移具有重要意义。

研究人员前期比较了GES-1和SGC-7901两种细胞系之间的差异表达基因,选择PCDHGA9基因进行下一步的研究。
 
内外源实验发现,PCDHGA9能够抑制癌细胞的侵袭及转移。聚类分析表明PCDHGA9通过介导Wnt/β-catenin信号通路和TGF-β通路抑制上皮-间质转化(EMT)过程。激光共聚焦实验及Western blotting实验显示PCDHGA9能够抑制β-catenin的核转运,调节TCF(T细胞因子)/LEF(淋巴增强因子)的转录活性,并直接影响TGF-β/Smad2/3通路的信号转导过程,促进粘附复合物的形成,弱化TGF-β的作用,并阻断Wnt信号通路的激活。此外,PCDHGA9的表达受甲基化的调控,这也与不良的临床预后紧密相关。

该研究阐明了PCDHGA9抑制GC中EMT过程及GC转移的分子机制,为鉴定GC转移提供了新的理论基础,并为改善转移性GC提供新的治疗靶标。

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    2020-05-28 mjldent
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    2020-05-26 docwu2019
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    2020-04-16 cy0328

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