HOXD3 is a sequence-specific transcription factor that plays critical roles in both development and cancer progression. As part of the developmental regulatory system, HOXD3 provides cells with positional identities along the anterior-posterior axis and regulates embryonic morphogenesis 1. In cancer contexts, HOXD3 functions as a metastasis-promoting gene through transcriptional regulation of invasion-related pathways. Overexpression of HOXD3 in lung cancer cells induces coordinate expression of metastasis-related genes, including loss of E-cadherin, upregulation of integrins (α3, β3, αvβ3), and increased production of matrix metalloproteinase-2 and urokinase-plasminogen activator, ultimately enhancing cell motility, invasion, and metastatic potential 1. In hepatocellular carcinoma, HOXD3 directly targets the VEGFR promoter region to increase VEGFR expression, promoting angiogenesis and metastasis 2. The gene is subject to epigenetic regulation, with DNA methylation patterns affecting its expression in renal cell carcinoma, where hypermethylation and low expression correlate with poor patient survival 3. HOXD3 has been identified as a potential biomarker and therapeutic target across multiple cancer types, including ovarian cancer where genetic variants near HOXD3 are associated with disease risk 45.