Institute of Pathogenic Biology, Hengyang Medical College, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control; Hunan Province Innovative Training Base for Postgraduates, University of South China and Nanyue Biopharmaceutical Co. Ltd., Hengyang 421001, Hunan, China.
School of Nursing, University of South China, Hengyang 421001, Hunan, China.
Pathog Dis. 2022 Aug 17;80(1). doi: 10.1093/femspd/ftac025.
Tumor necrosis factor-α-inducing protein (Tipα) is a newly identified toxin that promotes the inflammation and carcinogenesis caused by Helicobacter pylori. However, its mechanism of pathogenesis is still unclear. To investigate the carcinogenic mechanisms of Tipα, SGC7901 cells and SGC7901-derived cancer stem-like cells (CSCs) were stimulated by recombinant Tipα with or without Wnt/β-catenin signaling inhibitor XAV939. qRT-PCR and Western blotting were employed to detect expression of epithelial-mesenchymal transition (EMT), CSCs markers and downstream target genes of this signaling pathway. The cell migration ability was measured by wound healing assay and transwell assay. Our results indicated that Tipα promoted CSC properties of SGC7901 spheroids, including increased expression of CSC specific surface markers CD44, Oct4 and Nanog and an increased capacity for self-renewal. Tipα activated Wnt/β-catenin signaling in both SGC7901 cells or CSCs. Furthermore, Tipα induced the EMT and increased the expressions of downstream target genes of this signaling, including c-myc, cyclin D1 and CD44. However, XAV939 pretreatment inhibited Tipα-induced EMT and CSC properties in SGC7901 cells or CSCs. These results suggest that Tipα promotes EMT and CSC-like properties in gastric cancer cells through activation of Wnt/β-catenin signaling pathway, thereby accelerating the progression of gastric cancer.
肿瘤坏死因子-α诱导蛋白（Tipα）是一种新发现的毒素，可促进幽门螺杆菌引起的炎症和癌变。然而，其发病机制尚不清楚。为了研究 Tipα的致癌机制，用重组 Tipα刺激 SGC7901 细胞和 SGC7901 衍生的癌症干细胞样细胞（CSCs），并用 Wnt/β-catenin 信号抑制剂 XAV939 处理。采用 qRT-PCR 和 Western blot 检测上皮间质转化（EMT）、CSC 标志物和该信号通路下游靶基因的表达。通过划痕愈合实验和 Transwell 实验检测细胞迁移能力。结果表明，Tipα促进了 SGC7901 球体的 CSC 特性，包括增加了 CSC 特异性表面标志物 CD44、Oct4 和 Nanog 的表达以及自我更新能力。Tipα激活了 SGC7901 细胞或 CSCs 中的 Wnt/β-catenin 信号。此外，Tipα诱导 EMT，并增加了该信号下游靶基因的表达，包括 c-myc、cyclin D1 和 CD44。然而，XAV939 预处理抑制了 Tipα诱导的 SGC7901 细胞或 CSCs 中的 EMT 和 CSC 特性。这些结果表明，Tipα通过激活 Wnt/β-catenin 信号通路促进胃癌细胞中的 EMT 和 CSC 样特性，从而加速胃癌的进展。
