RUNX3 in oncogenic and anti-oncogenic signaling in gastrointestinal cancers.

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.