Products Cited in Publications Worldwide A pathological role of O-GlcNAcylation-driven TR11B production and function in lung adenocarcinoma

A pathological role of O-GlcNAcylation-driven TR11B production and function in lung adenocarcinoma

Qiu, Shiyu; Ma, Lifang; Yu, Keke; Xu, Xin; Zhang, Xiao; Yu, Wenjun; Wang, Kai; Tian, Xiaoting; Miao, Yayou; Wang, Yikun

DOI: PMID:

Abstract

Cytokines link inflammation to tumorigenesis, but the role of post-translational modifications in regulating their function within the extra-tumoral environment remains poorly defined. Here, we identify tumor-derived tumor necrosis factor (TNF) receptor superfamily member 11B (TR11B) as a key driver of lung adenocarcinoma (LUAD) progression and therapeutic resistance. Mechanistically, O-GlcNAc transferase (OGT)-mediated O-GlcNAcylation at serine 151 stabilizes TR11B and facilitates its interaction with the membrane protein EPS15 homology domain-containing protein 1 (EHD1), promoting cyclin dependent kinase 2 (CDK2) phosphorylation and progression. Clinically, elevated O-GlcNAcylated TR11B correlates with advanced LUAD. Genetic deletion of Ogt suppresses tumor development in LUAD mouse models. Importantly, , an U.S. Food and Drug Administration (FDA)-approved drug, inhibits O-GlcNAcylation and exerts antitumor effects. These findings reveal a pathological role for cytokine O-GlcNAcylation in LUAD and identify this axis as a potential therapeutic target.

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