Li Xiaofei, Zhang Haibo, Dong Jianan, Wang Juan
Department of Obstetrics and Gynecology, The Fourth Hospital of Hebei Medical University, No.12, Health Road, Shijiazhuang City, 050011, Hebei Province, China.
Sci Rep. 2025 Jan 9;15(1):1535. doi: 10.1038/s41598-025-85445-w.
This article focusing on examining the function and further, molecular function of SHP2 in ovarian cancer (OC). For the molecular mechanism, bioinformatics was applied to study the specifically expressed genes in ovarian cancer ; the western blotting was applied to identify the EGF, p-SHP2, ZEB1, and E-Cadherin expressions in ovarian cancer tissue and pair adjacent tissue; then SKOV3 cells were treated with EGF and infected with E-Cadherin overexpression lentivirus, and then cells were treated with benzyl butyl phthalate and IRS-1 respectively. Detection of expression of p-SHP2, ZEB1, E-Cadherin, α3-integrin, p-Src, p-SMAD2, Snail, Slug and SKOV3 cells of migration and invasion abilities were detected using Western blot method and cell scratch assay and Transwell assay; Progression of ovarian cancer was detected using subcutaneous tumor transplantation assay in nude mice and HE staining method and immunocyto. The bioinformatics analysis results suggested that SHP2 is highly specifically expressed and E-Cadherin, which is low specifically expressed in ovarian cancer tissues, while EGF, p-SHP2 or ZEB1 are highly expressed and E-Cadherin is low expressed in ovarian cancer tissues; Overexpression of E-Cadherin could reduce the expressions of p-SHP2, ZEB1, α3-integrin, p-Src, p-SMAD2, Snail and Slug might has roles in alleviating the ovarian cancer development and decreasing the levels of p-SHP2 and ZEB1 in tumor samples. And E-Cadherin overexpression reduced the migration and invasion ability of SKOV3 cells. SHP2 tyrosine phosphatase enhances the ovarian cancer cells' motility and invasiveness by upregulation of the integrin/E-Cadherin switch through ZEB1 signal.
本文着重研究SHP2在卵巢癌(OC)中的功能以及进一步的分子功能。对于分子机制,应用生物信息学研究卵巢癌中特异性表达的基因;应用蛋白质印迹法鉴定卵巢癌组织及其配对的相邻组织中表皮生长因子(EGF)、磷酸化SHP2(p-SHP2)、锌指E盒结合蛋白1(ZEB1)和E-钙黏蛋白的表达;然后用EGF处理SKOV3细胞并感染E-钙黏蛋白过表达慢病毒,接着分别用邻苯二甲酸丁苄酯和胰岛素受体底物1(IRS-1)处理细胞。采用蛋白质印迹法、细胞划痕试验和Transwell试验检测p-SHP2、ZEB1、E-钙黏蛋白、α3整合素、磷酸化Src(p-Src)、磷酸化SMAD2、Snail、Slug的表达以及SKOV3细胞的迁移和侵袭能力;采用裸鼠皮下肿瘤移植试验、苏木精-伊红(HE)染色法和免疫细胞化学法检测卵巢癌的进展。生物信息学分析结果表明,SHP2在卵巢癌组织中高度特异性表达,而E-钙黏蛋白在卵巢癌组织中低特异性表达,同时EGF、p-SHP2或ZEB1在卵巢癌组织中高表达而E-钙黏蛋白低表达;E-钙黏蛋白的过表达可降低p-SHP2、ZEB1、α3整合素、p-Src、p-SMAD2、Snail和Slug的表达,可能在减轻卵巢癌发展以及降低肿瘤样本中p-SHP2和ZEB1水平方面发挥作用。并且E-钙黏蛋白的过表达降低了SKOV3细胞的迁移和侵袭能力。SHP2酪氨酸磷酸酶通过ZEB1信号上调整合素/E-钙黏蛋白转换,增强卵巢癌细胞的运动性和侵袭性。