GALNTs in cancer: Driving tumor progression and opening a new therapeutic frontier

The human GALNT family consists of 20 isoenzymes that initiate mucin-type O-glycosylation. These enzymes catalyze the transfer of N-acetylgalactosamine to serine or threonine residues on protein substrates. This process generates Tn antigens, which serve as the foundation for further glycan elongation. Altered expression of specific GALNT isoenzymes correlates with cancer prognosis. These changes directly modulate malignant phenotypes, including proliferation, migration, invasion, and metastasis. Such effects are mediated through the regulation of epithelial-mesenchymal transition-related molecules. GALNT family members exhibit distinct expression patterns across cancer types. They function as either oncogenes or tumor suppressors depending on the cellular context. Their roles extend to remodeling the tumor immune microenvironment and influencing therapeutic response. Given their functional diversity and clinical relevance, GALNTs represent promising biomarkers and therapeutic targets. Elucidating their regulatory mechanisms will provide a molecular foundation for developing precision-targeted cancer therapies.