HOXC10 is a homeobox transcription factor that functions as a sequence-specific DNA-binding activator of RNA polymerase II-dependent gene expression 1. Originally characterized for roles in developmental processes including limb morphogenesis and motor neuron differentiation, HOXC10 is now recognized as a critical oncogenic regulator dysregulated across multiple cancer types 1. Mechanistically, HOXC10 promotes cancer progression through multiple pathways. In glioma, HOXC10 directly binds promoter regions of immunosuppressive genes including PD-L2 and TDO2, driving their expression 2. It also activates oncogenic signaling cascades; in KRAS-mutant lung cancer, HOXC10 activates the NOD1/ERK axis to reprogram epithelial-mesenchymal transition and promote bone metastasis 3. Additionally, HOXC10 transcriptionally upregulates VEGFA through interaction with histone methyltransferases PRMT5 and WDR5, promoting tumor angiogenesis 4. In glioma microenvironments, HOXC10 enhances CCL2 expression to recruit and polarize immunosuppressive M2-type macrophages 5. Clinically, HOXC10 upregulation correlates with poor prognosis across glioma, thyroid cancer, and lung adenocarcinoma, with elevated expression associated with reduced overall survival in multiple independent datasets 26. HOXC10 knockdown inhibits cell proliferation, migration, and invasion while promoting apoptosis 25, supporting HOXC10 as a potential therapeutic target, particularly in combination with pathway inhibitors or immunotherapy strategies.