Department of Oncology surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Gastrointestinal surgery, The First Affiliated Hospital of Sun Yat sen University, Guangzhou, China.
J Cell Mol Med. 2020 Dec;24(24):14217-14230. doi: 10.1111/jcmm.16038. Epub 2020 Oct 30.
Six-Transmembrane Epithelial Antigene of the Prostate 1 (STEAP1) is associated with the occurrence and development of cancer. This study aimed to clarify the role of STEAP1 in gastric cancer tumour growth and metastasis, as well as its molecular mechanism of action.Statistical methods were used for clinical data analysis. Protein expression was detected using immunohistochemistry(IHC). The mRNA and protein expression in the cell cultures were detected using reverse transcription-polymerase chain reaction(RT-PCR) and western blot analysis. Overexpression and silencing models were constructed using plasmid and lentivirus transfection. To detect cell proliferation in vitro, Cell Counting Kit-8(CCK-8), flow cytometry and colony formation assays were used; transwell and wound healing assays were used to detect cell migration and invasion;For in vivo experiments, nude BALB/c mice were used for detecting subcutaneous tumorigenesis and intraperitoneal implantation. In the results,we found STEAP1 was overexpressed in gastric cancer tissues and cell lines. Single-factor and Cox analyses showed that STEAP1 gene expression level correlated with poor prognosis. Up-regulation of STEAP1 increased cell proliferation, migration and invasion, which decreased after STEAP1 was knocked down. These changes were achieved via the activation of the AKT/FoxO1 pathway and epithelial-mesenchymal transformation (EMT). The in vivo animal experiments showed that STEAP1 knock down, resulted in a decrease in the subcutaneous tumour and peritoneal tumour formation.
六跨膜上皮抗原 1(STEAP1)与癌症的发生和发展有关。本研究旨在阐明 STEAP1 在胃癌肿瘤生长和转移中的作用及其作用机制。采用统计方法对临床资料进行分析。采用免疫组织化学(IHC)检测蛋白表达。采用逆转录-聚合酶链反应(RT-PCR)和蛋白质印迹分析检测细胞培养物中的 mRNA 和蛋白表达。采用质粒和慢病毒转染构建过表达和沉默模型。体外检测细胞增殖采用细胞计数试剂盒-8(CCK-8)、流式细胞术和集落形成实验;采用 Transwell 和划痕愈合实验检测细胞迁移和侵袭;体内实验采用裸鼠进行皮下肿瘤生成和腹腔内植入实验。结果发现,STEAP1 在胃癌组织和细胞系中高表达。单因素和 Cox 分析表明,STEAP1 基因表达水平与预后不良相关。STEAP1 的上调增加了细胞的增殖、迁移和侵袭,而在 STEAP1 被敲低后则减少。这些变化是通过激活 AKT/FoxO1 通路和上皮-间充质转化(EMT)实现的。体内动物实验表明,STEAP1 敲低导致皮下肿瘤和腹膜肿瘤形成减少。