The effect and molecular mechanism of N-Acetylglucosamine transferase-V in the pathogenesis of cancers.

N-Acetylglucosaminyltransferase V (GnT-V) is a pivotal glycosyltransferase catalyzing the formation of β1-6 branched N-glycans, a structural modification intimately linked to cancer malignancy. While elevated GnT-V expression correlates with metastasis in breast, gastric, and colorectal cancers, its function is context-dependent, predicting distinct outcomes in lung and bladder cancers. Crucially, the oncogenic potential of GnT-V is not isolated but is dynamically regulated by its competitive interplay with GnT-III and cooperation with α1,6-fucosyltransferase 8 (Fut8). Distinct from previous summaries, this review systematically dissects the molecular signaling networks driving these pathologies. Beyond well-known pathways like Wnt/β-catenin and receptor stabilization (EGFR, HER-2), we highlight emerging evidence regarding the role of GnT-V in promoting resistance to anoikis and facilitating immune evasion. Furthermore, we detail how GnT-V orchestrates the epithelial-mesenchymal transition (EMT) and cytoskeletal remodeling via the RhoA/Rac1 axis. By integrating these signaling networks with the enzyme's regulatory environment, we provide a comprehensive roadmap of GnT-V pathogenesis and propose that targeting the GnT-V/GnT-III balance represents a promising strategy for precise cancer diagnosis and therapy.