The role and molecular mechanism of Trop2 induced epithelial-mesenchymal transition through mediated β-catenin in gastric cancer
The role and molecular mechanism of Trop2 induced epithelial-mesenchymal transition through mediated β-catenin in gastric cancer
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Trop2介导的β-连环蛋白诱导上皮间质转化在胃癌中的作用和分子机制
DOI：
10.1002/cam4.1934
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发表时间：
2019-03-01
期刊：
影响因子：
4
通讯作者：
Feng, Zhenqing
中科院分区：
文献类型：
--
作者：
Zhao, Wei;Jia, Lizhou;Feng, Zhenqing
本研究阐明了在胃癌（GC）中Trop2与β-连环蛋白结合时在肿瘤侵袭以及促进上皮 - 间质转化（EMT）方面的潜在作用。通过多种实验方法检测了Trop2在促进胃癌细胞EMT中的作用。此外，通过体内和体外实验研究了Trop2促进EMT的潜在分子机制。通过免疫组化（IHC）检测了248例胃癌组织和86例匹配的癌旁组织中Trop2表达与肿瘤转移状态的关系。Trop2促进胃癌的转移并诱导EMT。同时，在胃癌细胞中转化生长因子-β1诱导的EMT模型中也发现Trop2和间质标志物的蛋白水平升高。重要的是，Trop2与β - 连环蛋白物理结合并激活它以促进EMT；此外，Trop2增加了β - 连环蛋白在细胞核中的积累，从而加速胃癌细胞的转移。抑制胃癌细胞中Trop2的表达可阻止胃癌细胞在体内的迁移和侵袭。Trop2+/波形蛋白+在胃癌组织中的表达高于匹配的癌旁组织，并且胃癌中Trop2+/波形蛋白+的表达与分化程度、TNM分期和远处转移有关。这些数据揭示了Trop2在EMT和胃癌转移中的一种新的调控网络，表明Trop2可作为诱导胃癌EMT和转移的有用标志物，这可能有助于更好地理解胃癌的发病机制。
The present study elucidates the potential role of Trop2 in tumor invasion and the promotion of epithelial-mesenchymal transition (EMT) when binding beta-catenin in GC. The role of Trop2 in promoting EMT in GC cells was examined by a variety of experimental assays. Moreover, the underlying molecular mechanism of Trop2 in promoting EMT was studied by in vivo and in vitro assays. The Trop2 expression in relation to tumor metastasis status was detected by IHC in 248 cases of GC tissues and 86 cases of matched adjacent tissues. Trop2 promoted the metastasis and induces EMT in GC. Meanwhile, the elevated protein levels of Trop2 and mesenchymal markers were also found in the TGF-beta 1-induced EMT model in GC cells. Importantly, Trop2 physically bound and activated beta-catenin to promote EMT; moreover, Trop2 increased the accumulation of beta-catenin in the nucleus to accelerate metastasis in GC cells. Inhibition of Trop2 expression in GC cells prevented the migration and invasion of GC cells in vivo. Trop2+/vimentin+ expression was higher in GC tissues than that in matched adjacent tissues, and Trop2+/vimentin+ expression in GC was associated with the differentiation, TNM stage, and distant metastases. These sets of data reveal a novel regulatory network of Trop2 in EMT and GC metastasis, suggesting Trop2 as a useful marker for inducing EMT and metastasis of GC, which may help to lead a better understanding of the pathogenesis of the GC.