Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
Department of Medicinal Chemistry, College of Pharmacy, Army Medical University, Chongqing, 400038, China.
Cancer Lett. 2022 Aug 28;542:215764. doi: 10.1016/j.canlet.2022.215764. Epub 2022 May 31.
Gastric cancer (GC) is the fourth leading cause of cancer-related death. Its poor prognosis is attributed to unclear pathogenesis. Currently, the most widely accepted model for elucidating the mechanism of GC is the Correa cascade, which covers several histological lesions of the gastric mucosa. GC stem cells (CSCs) are crucial for oncogenesis in the Correa cascade and GC progression. As Helicobacter pylori (H. pylori) is the etiological factor in the Correa cascade, growing evidence suggests that enhancement of gastric stem cell-like properties and increase in CSCs correlate with H. pylori infection. In this paper, we review recent studies that present pathogenic mechanisms by which H. pylori induces gastric stem cell-like properties and CSCs, which may supplement the existing Correa model of GC. First, the dysfunction of developmental signaling pathways associated with H. pylori infection leads to the enhancement of gastric stemness. Second, H. pylori infection promotes alteration of the gastric mucosal microenvironment. In addition, epithelial-mesenchymal transition (EMT) may contribute to H. pylori-induced gastric stemness. Taken together, understanding these pathogeneses will provide potential therapeutic targets for the treatment of CSCs and malignant GC in H. pylori induced-Correa cascade of GC.
胃癌（GC）是癌症相关死亡的第四大主要原因。其预后不良归因于发病机制不明确。目前，用于阐明 GC 机制的最广泛接受的模型是 Correa 级联，它涵盖了胃黏膜的几种组织学病变。GC 干细胞（CSCs）对于 Correa 级联中的肿瘤发生和 GC 进展至关重要。由于幽门螺杆菌（H. pylori）是 Correa 级联中的病因，越来越多的证据表明，胃干细胞样特性的增强和 CSCs 的增加与 H. pylori 感染相关。在本文中，我们回顾了最近的研究，这些研究提出了 H. pylori 诱导胃干细胞样特性和 CSCs 的发病机制，这可能补充现有的 GC Correa 模型。首先，与 H. pylori 感染相关的发育信号通路的功能障碍导致胃干细胞功能增强。其次，H. pylori 感染促进胃黏膜微环境的改变。此外，上皮-间充质转化（EMT）可能有助于 H. pylori 诱导的胃干细胞功能。总之，了解这些发病机制将为治疗 H. pylori 诱导的 Correa 级联 GC 中的 CSCs 和恶性 GC 提供潜在的治疗靶点。
