Vitamin K-dependent gamma-carboxyglutamic acid protein 1 promotes pancreatic ductal adenocarcinoma progression through stabilizing oncoprotein KRAS and tyrosine kinase receptor EGFR

Zheng Wu; Qing Ye; Shan Zhang; Li-Peng Hu; Xiao-Qi Wang; Lin-Li Yao; Lei Zhu; Shu-Yu Xiao; Zong-Hao Duan; Xue-Li Zhang; Shu-Heng Jiang; Zhi-Gang Zhang; De-Jun Liu; Dong-Xue Li; Xiao-Mei Yang

doi:10.1002/ctm2.70191

Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (1) : e70191 DOI: 10.1002/ctm2.70191

RESEARCH ARTICLE

Vitamin K-dependent gamma-carboxyglutamic acid protein 1 promotes pancreatic ductal adenocarcinoma progression through stabilizing oncoprotein KRAS and tyrosine kinase receptor EGFR

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Abstract

	•PRRG1 is identified as the transmembrane Gla protein mediating PDAC malignancy.
	•PRRG1 recruits and induces self-ubiquitination of membrane-anchoring E3 ligase NEDD4.
	•PRRG1 exerts a protective role toward KRAS and EGFR by inhibiting NEDD4.
	•The anticoagulant warfarin can be utilized to inhibit PRRG1 and PDAC advancement.

Keywords

KRAS / NEDD4 E3 ligases / pancreatic cancer / PRRG1 / vitamin K-dependent carboxylation

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Zheng Wu, Qing Ye, Shan Zhang, Li-Peng Hu, Xiao-Qi Wang, Lin-Li Yao, Lei Zhu, Shu-Yu Xiao, Zong-Hao Duan, Xue-Li Zhang, Shu-Heng Jiang, Zhi-Gang Zhang, De-Jun Liu, Dong-Xue Li, Xiao-Mei Yang. Vitamin K-dependent gamma-carboxyglutamic acid protein 1 promotes pancreatic ductal adenocarcinoma progression through stabilizing oncoprotein KRAS and tyrosine kinase receptor EGFR. Clinical and Translational Medicine, 2025, 15(1): e70191 DOI:10.1002/ctm2.70191

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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.