Zhao Yi, Hu Fang, Wang Qizhi
Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui 233004, China.
Department of Hematology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui 233004, China.
Heliyon. 2023 Jul 14;9(7):e18289. doi: 10.1016/j.heliyon.2023.e18289. eCollection 2023 Jul.
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.
胃癌是一种死亡率和发病率都很高的恶性肿瘤。本研究旨在探讨Cortactin在体外和体内对胃癌进展的作用及分子机制。来自TCGA的生物信息学分析显示，Cortactin在胃癌样本中高表达，Cortactin水平高的患者生存率较差。随后，我们通过收集患者样本进行免疫组化、WB、qRT-PCR、细胞转染、细胞侵袭和转移实验，并在裸鼠体内构建肿瘤异种移植模型，研究了A在胃癌中的具体作用机制。Cortactin的过表达抑制了AGS细胞的凋亡，增强了细胞增殖和迁移能力，而MMP2或MMP9的敲低则逆转了这些活性。相反，Cortactin的缺失诱导了SGC7901细胞的凋亡，抑制了细胞生长和转移，而MMP2或MMP9的过表达则抑制了这些行为。此外，Cortactin的上调激活了ERK通路。体内研究表明，Cortactin的过表达促进了肿瘤生长，增加了Ki67表达，降低了caspase 3表达，而ERK抑制剂处理则逆转了这些作用。总之，Cortactin在胃癌中作为癌基因发挥作用，并通过ERK/MMP2/MMP9信号通路发挥其功能。
