https://ror.org/02crff812 Institute of Molecular Cancer Research, University of Zürich, Zürich, Switzerland.
https://ror.org/02crff812 Institute of Molecular Cancer Research, University of Zürich, Zürich, Switzerland
Life Sci Alliance. 2024 Aug 27;7(11). doi: 10.26508/lsa.202402783. Print 2024 Nov.
infection predisposes carriers to a high risk of developing gastric cancer. The cell-of-origin of antral gastric cancer is the Lgr5 stem cell. Here, we show that infection of antrum-derived gastric organoid cells with increases the expression of the stem cell marker Lgr5 as determined by immunofluorescence microscopy, qRT-PCR, and Western blotting, both when cells are grown and infected as monolayers and when cells are exposed to in 3D structures. exposure increases stemness properties as determined by spheroid formation assay. Lgr5 expression and the acquisition of stemness depend on a functional type IV secretion system (T4SS) and at least partly on the T4SS effector CagA. The pharmacological inhibition or genetic ablation of NF-κB reverses the increase in Lgr5 and spheroid formation. Constitutively active Wnt/β-catenin signaling because of inactivation exacerbates -induced Lgr5 expression and stemness, both of which persist even after eradication of the infection. The combined data indicate that has stemness-inducing properties that depend on its ability to activate NF-κB signaling.
感染使携带者面临罹患胃癌的高风险。胃窦癌的细胞起源是 Lgr5 干细胞。在这里，我们发现幽门螺杆菌感染胃窦来源的胃类器官细胞后，通过免疫荧光显微镜、qRT-PCR 和 Western blot 检测，无论是在单层细胞培养和感染时，还是在 3D 结构中暴露于 时，干细胞标志物 Lgr5 的表达均增加。幽门螺杆菌暴露可通过球体形成试验确定增加干细胞特性。Lgr5 表达和获得干性依赖于功能性 IV 型分泌系统 (T4SS)，至少部分依赖于 T4SS 效应因子 CagA。NF-κB 的药理学抑制或基因敲除可逆转 Lgr5 的增加和球体形成。由于 失活导致的组成性激活 Wnt/β-catenin 信号转导加剧了 诱导的 Lgr5 表达和干性，即使在感染消除后，这些仍持续存在。综合数据表明，幽门螺杆菌具有干性诱导特性，这取决于其激活 NF-κB 信号的能力。
