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CLDN6 promotes tumor progression through the YAP1-snail1 axis in gastric cancer.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-12-11 , DOI: 10.1038/s41419-019-2168-y Site Yu 1 , Yeqian Zhang 1 , Qing Li 2 , Zizhen Zhang 1 , Gang Zhao 1 , Jia Xu 1
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-12-11 , DOI: 10.1038/s41419-019-2168-y Site Yu 1 , Yeqian Zhang 1 , Qing Li 2 , Zizhen Zhang 1 , Gang Zhao 1 , Jia Xu 1
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Claudin6 (CLDN6), a member of the tight junction family, is a molecule involved in intercellular adhesion, acting as a physical barrier that prevents solutes and water from freely passing through the extracellular space. CLDN6 has important biological functions, and its abnormal expression is associated with Hepatitis C infection. However, there is limited research regarding its role in gastric cancer. In this study, we found that the expression of CLDN6 mRNA and protein was upregulated in gastric cancer cell lines and tissues, which indicated poor prognosis. Both in vitro and in vivo experiments showed that abnormal CLDN6 expression was associated with enhanced proliferation and invasion abilities of gastric cancer. CLDN6 reduced the phosphorylation of LATS1/2 and YAP1 by interacting with LATS1/2 in the Hippo signaling pathway. Thus, CLDN6 affected the entry of YAP1 into the nucleus, causing changes in downstream target genes. Moreover, YAP1 interacted with snail1 to affect the process of EMT and enhanced the invasive ability of GC cells. Collectively, CLDN6 promoted the proliferation and invasive ability of gastric cancer by affecting YAP1 and YAP1-snail1 axis.
中文翻译：
CLDN6通过YAP1-snail1轴促进胃癌的肿瘤进展。
Claudin6（CLDN6）是紧密连接家族的成员，是一种参与细胞间黏附的分子，充当防止溶质和水自由通过细胞外空间的物理屏障。CLDN6具有重要的生物学功能，其异常表达与丙型肝炎感染有关。然而，关于其在胃癌中的作用的研究还很有限。在这项研究中，我们发现CLDN6 mRNA和蛋白的表达在胃癌细胞系和组织中上调，表明预后不良。体外和体内实验均表明，CLDN6表达异常与胃癌的增殖和侵袭能力增强有关。CLDN6通过与Hippo信号通路中的LATS1 / 2相互作用来减少LATS1 / 2和YAP1的磷酸化。因此，CLDN6影响YAP1进入细胞核，导致下游靶基因发生变化。此外，YAP1与snail1相互作用以影响EMT的过程并增强GC细胞的侵袭能力。总的来说，CLDN6通过影响YAP1和YAP1-snail1轴来促进胃癌的增殖和侵袭能力。
更新日期：2019-12-11
中文翻译：
CLDN6通过YAP1-snail1轴促进胃癌的肿瘤进展。
Claudin6（CLDN6）是紧密连接家族的成员，是一种参与细胞间黏附的分子，充当防止溶质和水自由通过细胞外空间的物理屏障。CLDN6具有重要的生物学功能，其异常表达与丙型肝炎感染有关。然而，关于其在胃癌中的作用的研究还很有限。在这项研究中，我们发现CLDN6 mRNA和蛋白的表达在胃癌细胞系和组织中上调，表明预后不良。体外和体内实验均表明，CLDN6表达异常与胃癌的增殖和侵袭能力增强有关。CLDN6通过与Hippo信号通路中的LATS1 / 2相互作用来减少LATS1 / 2和YAP1的磷酸化。因此，CLDN6影响YAP1进入细胞核，导致下游靶基因发生变化。此外，YAP1与snail1相互作用以影响EMT的过程并增强GC细胞的侵袭能力。总的来说，CLDN6通过影响YAP1和YAP1-snail1轴来促进胃癌的增殖和侵袭能力。
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