Fischer Anne-Sophie, Sigal Michael
Department of Hepatology and Gastroenterology, Charité University Medicine, 10117 Berlin, Germany.
Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
Biomedicines. 2019 Jun 19;7(2):44. doi: 10.3390/biomedicines7020044.
The Wnt signaling pathway is one of the most prominent developmental signals. In addition to its functions in development, there is emerging evidence that it is also crucial for various organ functions in adult organisms, where Wnt signaling controls tissue stem cell behavior, proliferation and differentiation. Deregulation of Wnt signaling is involved in various pathological conditions and has been linked to malignant tissue transformation in different organ systems. The study of the Wnt signaling pathway has revealed a complex regulatory network that tightly balances the quality and strength of Wnt signaling in tissues. In this context, R-spondins are secreted proteins that stabilize Wnt receptors and enhance Wnt signaling. In this review we focus on new insights into the regulatory function of Wnt and R-spondin signaling in the stomach. In addition to its function in the healthy state, we highlight the connection between Wnt signaling and infection with , a pathogen that colonizes the stomach and is the main risk factor for gastric cancer. In addition to experimental data that link Wnt signaling to carcinogenesis, we discuss that Wnt signaling is affected in a substantial proportion of patients with gastric cancer, and provide examples for potential clinical implications for altered Wnt signaling in gastric cancer.
Wnt信号通路是最为显著的发育信号之一。除了在发育过程中的功能外，越来越多的证据表明，它对成年生物体的各种器官功能也至关重要，在成年生物体中，Wnt信号控制组织干细胞行为、增殖和分化。Wnt信号失调涉及多种病理状况，并与不同器官系统的恶性组织转化有关。对Wnt信号通路的研究揭示了一个复杂的调控网络，该网络紧密平衡组织中Wnt信号的质量和强度。在这种情况下，R-spondins是分泌蛋白，可稳定Wnt受体并增强Wnt信号。在本综述中，我们重点关注Wnt和R-spondin信号在胃中的调控功能的新见解。除了其在健康状态下的功能外，我们还强调了Wnt信号与幽门螺杆菌感染之间的联系，幽门螺杆菌是一种定植于胃中的病原体，也是胃癌的主要危险因素。除了将Wnt信号与致癌作用联系起来的实验数据外，我们还讨论了相当一部分胃癌患者的Wnt信号受到影响，并提供了胃癌中Wnt信号改变的潜在临床意义的实例。
