Abstract

ST6Gal1 (α2,6-sialyltransferase1), the primary glycosyltransferase catalyzing α2,6-sialylation of N-glycans, plays a pivotal role in the progression of various human cancers. However, the role of ST6Gal1-mediated α2,6-sialylation in human esophageal squamous cell carcinoma (ESCC) remains poorly understood. In this study, we established ST6Gal1 knockdown (Kyse450-KD) and overexpressed (Kyse150-OE) ESCC cell models to investigate its functional significance. Cell viability assays and western blot analysis show that ST6Gal1 deficiency sensitizes ESCC cells to IFN-γ-induced apoptosis. ST6Gal1 knockdown upregulated IFN-γ receptor 1(IFN-γR1) expression and augmented downstream JAK/STAT signaling, whereas ST6Gal1 overexpression elicited the opposite effects‌. Furthermore, dual luciferase reporter analysis demonstrated that STAT1 directly binds to and activates the IFN-γR1 promoter, establishing a potential feedback loop. Our findings demonstrate that ST6Gal1 governs ESCC resistance to IFN-γ by modulating the STAT1-dependent transcription of IFN-γR1.