ST6Gal

ST6Gal enzymes catalyze terminal α2,6-sialylation, with ST6GAL1 adding α2,6-linked sialic acid to N-glycosylated membrane receptors and regulating receptor structure, signaling, and cell phenotype^[1]. Mechanistically, ST6GAL1-mediated α2,6-sialylation modulates pathways involving MUC4β secretion, integrin β1/FAK signaling, PDGFRB activation, and Hippo pathway control in airway, trophoblastic, glioblastoma, and breast cancer models^[2][3][4][5]. In disease models, ST6GAL1 expression increases in PDAC under IL-1β/NF-κB and IL-6/STAT3 signaling, while α2,6-sialylation contributes to glioblastoma growth, gestational trophoblastic disease proliferation, and enzalutamide resistance in prostate cancer cells^[1][4][6][7]. Compared with related isoforms, ST6GAL1 and ST6GAL2 both control α2,6-sialic acid, but ST6GAL1 is broadly linked to membrane receptor sialylation, whereas ST6GAL2 shows distinct regulatory behavior and may compensate in prion-disease models^[8][9]. For experimental applications, the sialyltransferase inhibitor P-SiaFNEtoc partially reversed acquired enzalutamide resistance when combined with enzalutamide, supporting sialic acid blockade as a tool for testing ST6GAL1-linked drug-resistance mechanisms^[7].