CDX2 is an intestine-specific transcription factor that functions as a master regulator of intestinal epithelial development and homeostasis 1. As a sequence-specific DNA-binding protein, CDX2 activates transcription of multiple intestinal genes including sucrase-isomaltase, lactase-phlorizin hydrolase, claudin-2, and mucin-2, while preferentially binding methylated DNA sequences 2. In extraembryonic mesoderm, CDX2 dose-dependently regulates developmental gene networks, including VEGF and non-canonical WNT pathways critical for vascular development and allantoic elongation 3. Clinically, CDX2 functions as a tumor suppressor in colorectal cancer. CDX2 knockdown promotes colon cancer cell proliferation and tumor formation by suppressing Wnt/β-catenin signaling through transactivation of GSK-3β and Axin2 4. Conversely, CDX2 downregulation in low-mutation CRC variants drives metastasis through intrinsic WNT pathway activation independent of classical APC/CTNNB1 mutations 5. CDX2 loss or reduction is frequently observed in gastrointestinal cancers and pre-cancerous lesions such as Barrett's esophagus and intestinal metaplasia, suggesting loss of CDX2 expression may represent an early oncogenic event 6. Beyond CRC, CDX2 expression patterns help stratify pancreatic neuroendocrine tumors into prognostically distinct subgroups 7.