KRAS mutation-driven O-GlcNAcylation of CLDN18.2 enhances the progression of pancreatic cancer and reduces the efficacy of CLDN18.2-targeted therapy
KRAS mutations and hyperglycaemia drive O-GlcNAcylation of CLDN18.2 at its C-terminal T204 site. O-GlcNAcylated CLDN18.2 promotes poor prognosis and reduces the effectiveness of CLDN18.2-targeted therapies. Low dose MRTX1133 restores CLDN18.2 membrane localisation by reducing its O-GlcNAcylation and augments CLDN18.2-targeted therapy efficacy, offering a novel combinatorial strategy for KRAS-mutant PDAC.
Authors
- Jun Yu (ORCID: https://orcid.org/0000-0001-5009-2941)
- Yukuan Feng (ORCID: https://orcid.org/0009-0005-6497-0748)
- Xupeng Hou
- H. K. Sun (ORCID: https://orcid.org/0000-0002-7210-7187)
- M Chen
- Jihui Hao (ORCID: https://orcid.org/0000-0002-5598-6706)
- Hu Yu
- Tianxing Zhou (ORCID: https://orcid.org/0009-0006-0150-1343)
- C. Huang
- Antao Chang
- Lin Li
- Yifei Wang
- Tingting Xu
- Jing Liu
- Weiwei Bai
- Yongjie Xie
Institutions
- Chinese Academy of Sciences (CN)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- Fudan University Shanghai Cancer Center (CN)
- Zhejiang Cancer Hospital (CN)
- Beijing National Laboratory for Molecular Sciences (CN)
Publication Details
- Journal
- Gut
- Published
- 2026-01-09
- DOI
- https://doi.org/10.1136/gutjnl-2025-336277
- Primary Topic
- Glycosylation and Glycoproteins Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00