Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
J Cell Biochem. 2011 May;112(5):1243-9. doi: 10.1002/jcb.23047.
The reputation of RUNX3 as a strong candidate for a tumor suppressor originated from studies of gastric carcinogenesis and now extends to a variety of other human cancers. The RUNX3 transcription factor is a downstream effector of the TGF-β superfamily signaling pathway and has a critical role in the regulation of cell proliferation, cell death by apoptosis, and cell adhesion. Recently, RUNX3 was proposed as a gatekeeper linking oncogenic Wnt and anti-oncogenic TGF-β/BMPs signaling pathways in intestinal tumorigenesis in mouse and human. Also, loss of RUNX3 leading to elevated oncogenic Wnt activity was found to be a key event in inducing a precancerous state of the stomach. Chronic Helicobacter pylori infection is reported to inactivate RUNX3 in gastric carcinogenesis by multiple mechanisms. This "Prospect" focuses on our current understanding of the tumor suppressive functions of RUNX3 in the context of gastrointestinal cancer initiation and progression.
RUNX3 作为一种强有力的肿瘤抑制因子候选物的声誉源于对胃癌发生的研究，现在已扩展到多种其他人类癌症。RUNX3 转录因子是 TGF-β 超家族信号通路的下游效应因子，在调节细胞增殖、细胞凋亡和细胞黏附方面具有关键作用。最近，RUNX3 被提出作为连接致癌 Wnt 和抑癌 TGF-β/BMPs 信号通路的守门员，在小鼠和人类的肠道肿瘤发生中发挥作用。此外，研究发现 RUNX3 的缺失导致致癌 Wnt 活性升高，是诱导胃癌前期状态的关键事件。据报道，慢性幽门螺杆菌感染通过多种机制使 RUNX3 在胃癌发生中失活。这篇“展望”聚焦于我们目前对 RUNX3 在胃肠道癌发生和进展中的肿瘤抑制功能的理解。
