infection has been associated with gastric carcinogenesis. However, the precise involvement of LRP8, the low-density lipoprotein receptor-related protein 8, in pathogenesis and gastric cancer (GC) remains poorly understood. To investigate the potential role of LRP8 in infection and gastric carcinogenesis. Three-dimensional human-derived gastric organoids (hGO) and gastric cancer organoids (hGCO) were synthesized from the tissues obtained from human donors. In this work, multi-omics combined with studies were conducted to investigate the potential involvement of LRP8 in induced GC. We found that infection significantly upregulated the expression of LRP8 in human GC tissues, cells, organoids, and mouse gastric mucous. In particular, LRP8 exhibited a distinct enrichment in cancer stem cells (CSC). Functionally, silencing of LRP8 affected the formation and proliferation of tumor spheroids, while increased expression of LRP8 was associated with increased proliferation and stemness of GC cells and organoids. Mechanistically, LRP8 promotes the binding of E-cadherin to β-catenin, thereby promoting nuclear translocation and transcriptional activity of β-catenin. Furthermore, LRP8 interacts with the cytotoxin-associated gene A (CagA) to form the CagA/LRP8/β-catenin complex. This complex further amplifies -induced β-catenin nuclear translocation, leading to increased transcription of inflammatory factors and CSC markers. Clinical analysis demonstrated that abnormal overexpression of LRP8 is correlated with a poor prognosis and resistance to 5-Fluorouracil in patients with GC. Our findings provide valuable information on the molecular intricacies of -induced gastric carcinogenesis, offering potential therapeutic targets and prognostic markers for GC.

中文翻译：

---

幽门螺杆菌诱导的LRP8表达增强通过促进β-连环蛋白核易位驱动胃癌进展

感染与胃癌发生有关。然而，LRP8（低密度脂蛋白受体相关蛋白 8）在发病机制和胃癌 (GC) 中的确切参与仍知之甚少。探讨LRP8在感染和胃癌发生中的潜在作用。三维人源性胃类器官（hGO）和胃癌类器官（hGCO）是从人类捐赠者的组织中合成的。本工作通过多组学结合研究来探讨LRP8在诱导GC中的潜在参与作用。我们发现感染显着上调了人GC组织、细胞、类器官和小鼠胃粘膜中LRP8的表达。特别是，LRP8 在癌症干细胞 (CSC) 中表现出明显的富集。从功能上讲，LRP8 的沉默影响肿瘤球体的形成和增殖，而 LRP8 表达的增加与 GC 细胞和类器官的增殖和干细胞性增加相关。从机制上讲，LRP8促进E-钙粘蛋白与β-连环蛋白的结合，从而促进β-连环蛋白的核转位和转录活性。此外，LRP8 与细胞毒素相关基因 A (CagA) 相互作用，形成 CagA/LRP8/β-连环蛋白复合物。该复合物进一步放大β-连环蛋白核易位，导致炎症因子和 CSC 标记物的转录增加。临床分析表明，LRP8的异常过度表达与GC患者的不良预后和对5-氟尿嘧啶的耐药性相关。我们的研究结果提供了有关诱导胃癌发生的分子复杂性的宝贵信息，为胃癌提供了潜在的治疗靶点和预后标志物。