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Abstract：
Gastric cancer is a malignant tumor with high mortality and high incidence. This study aims to explore the function and molecular mechanism of Cortactin on gastric cancer progression in vitro and in vivo. A bioinformatics analysis from TCGA displayed that Cortactin was highly expressed in gastric cancer samples, and patients with a high Cortactin level had a worse survival rate. Subsequently, we investigated the specific mechanism of action of A in gastric cancer by collecting patient samples for immunohistochemistry, WB, qRT-PCR, cell transfection, cell invasion and metastasis, and constructing tumor xenografts in nude mice. Overexpression of Cortactin inhibited apoptosis and enhanced cellular proliferation and mobility in AGS cells, while those activities were reversed by the knockdown of MMP2 or MMP9. Conversely, the deletion of Cortactin induced apoptosis and suppressed cell growth and metastasis in SGC7901 cells, whereas those behaviors were inhibited by overexpression of MMP2 or MMP9. Additionally, the ERK pathway was activated by Cortactin upregulation. In vivo studies presented that overexpression of Cortactin promoted tumor growth, increased Ki67 expression, and reduced caspase 3 expression, which was reversed by ERK inhibitor treatment. In conclusion, Cortactin acted as an oncogene in gastric cancer and exerted its function by ERK/MMP2/MMP9 signaling pathway.
摘要：
胃癌是一种死亡率高、发病率高的恶性肿瘤。本研究旨在探讨Cortactin在体内外作用于胃癌进展的分子机制。来自TCGA的生物信息学分析显示，Cortactin在胃癌样本中高表达，高Cortactin水平的患者生存率较差。随后，我们通过收集患者样本进行免疫组织化学研究了A在胃癌中的具体作用机制，WB,qRT-PCR,细胞转染，细胞侵袭和转移，并在裸鼠体内构建肿瘤异种移植物。过表达Cortactin抑制AGS细胞凋亡，增强细胞增殖和迁移率，而这些活动被MMP2或MMP9的敲低所逆转。相反，Cortactin缺失诱导SGC7901细胞凋亡，抑制细胞生长和转移，而这些行为被MMP2或MMP9的过表达抑制。此外,ERK通路被Cortactin上调激活。体内研究表明，Cortactin的过表达促进了肿瘤的生长，Ki67表达增加，并降低caspase3的表达，ERK抑制剂治疗可逆转。总之,Cortactin在胃癌中作为癌基因，通过ERK/MMP2/MMP9信号通路发挥其功能。
