2. Academic Validation
  3. ST6Gal1 influences the esophageal squamous cell carcinoma resistance to IFN-γ by regulating the expression of IFN-γ receptor 1

ST6Gal1 influences the esophageal squamous cell carcinoma resistance to IFN-γ by regulating the expression of IFN-γ receptor 1

  • Biochim Biophys Acta Gen Subj. 2026 Jun;1870(6):130941. doi: 10.1016/j.bbagen.2026.130941.
Kaixin Zhang 1,  Nianzhu Zhang 2,  Yingshu Zhang 3,  Weiwei Zhao 1,  Shaobin Chen 4,  Wanli Song 5,  Wenzhe Li 6
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou, Guangdong 515041, China; Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, China.
  • 2 Clinical Laboratory, The Second Hospital of Dalian Medical University, Dalian, Liaoning Province 116023, China.
  • 3 Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, China.
  • 4 Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou, Guangdong 515041, China.
  • 5 Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou, Guangdong 515041, China; Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, China. Electronic address: [email protected].
  • 6 Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou, Guangdong 515041, China; Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, China. Electronic address: [email protected].
PMID: 41895538 DOI: 10.1016/j.bbagen.2026.130941
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.

Keywords

ESCC; IFN-γ resistance; IFN-γR1; ST6Gal1; a2,6-sialylation.

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