RUNX3 and neoplasm: The pathway is normally restrained by tumor suppressors including chromosome 8 open reading frame 4 (C8orf4)—which binds the NOTCH2 intracellular domain (N2ICD) to prevent nuclear translocation —and runt-related transcription factor 3 (RUNX3), which suppresses Jagged1-NOTCH signaling (398–400).