RUNX3 orchestrate tumor suppression in a various signaling pathway crosstalk.When RUNX3 is in its inactive form, the Runt domain, and activation domain are masked by inhibitory regions and domain, while some signaling pathways, including TGF-β, which is one of the most crucial pathways, activate RUNX3 through certain cofactors and change the conformation of it. Here, TGFB1 is linked to neoplasm.