Gastrin-17 induces gastric cancer cell epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway
Gastrin-17 induces gastric cancer cell epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway
复制标题
胃泌素 17 通过 Wnt/β-连环蛋白信号诱导胃癌细胞上皮间质转化
DOI：
10.1007/s13105-020-00780-y
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发表时间：
2021-02-24
影响因子：
3.4
通讯作者：
Xie, Yuan
中科院分区：
文献类型：
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作者：
Li, YaJie;Zhao, Yan;Xie, Yuan
胃癌（GC）是最常见的癌症之一，大多数患者常因肿瘤转移而死亡。近期的研究表明，胃泌素与胃癌转移密切相关。然而，这种关系背后的具体分子机制仍有待揭示。在本研究中，我们评估了胃泌素以及Wnt/β -连环蛋白抑制剂XAV939对SGC - 7901和MKN45胃癌细胞系上皮 - 间质转化（EMT）的影响，并且我们确定胃泌素 - 17显著降低了胃癌细胞中E - 钙黏蛋白的表达，并上调了Snail1和N - 钙黏蛋白的表达。此外，胃泌素17还以剂量依赖的方式显著增加了Wnt3α的表达。与这些结果一致的是，胃泌素 - 17以剂量依赖的方式促进胃癌细胞的侵袭、增殖和迁移，并且这些作用被XAV939所抑制。总之，这些结果表明胃泌素 - 17通过Wnt/β - 连环蛋白信号通路诱导胃癌细胞的上皮 - 间质转化、迁移和侵袭，这提示胃泌素/Wnt/β - 连环蛋白信号轴可能是预防胃癌转移的一个治疗靶点。
Gastric cancer (GC) is one of the most common cancers, with most patients often succumbing to death as a result of tumor metastasis. Recent work has demonstrated that gastrin is closely associated with GC metastasis. However, the specific molecular mechanisms underlying this relationship remain to be unveiled. In this study, we assessed the impact of gastrin and the Wnt/beta-catenin inhibitor XAV939 on the epithelial-mesenchymal transition (EMT) of the SGC-7901 and MKN45 GC cell lines, and we determined that gastrin-17 significantly decreased E-cadherin expression and upregulated the expression of Snail1 and N-cadherin in GC cells. In addition, gastrin 17 also significantly increased the expression of Wnt3 alpha in a dose-dependent manner. Consistent with these results, gastrin-17 promoted GC cell invasion, proliferation, and migration in a dose-dependent fashion, and these effects were inhibited by XAV939. Together, these results indicated that gastrin-17 induced GC cell EMT, migration, and invasion via the Wnt/beta-catenin signaling pathway, which suggests that this gastrin/Wnt/beta-catenin signaling axis may represent a therapeutic target for the prevention of GC metastasis.