Evidence map›Paper›PMID 41634678›Full record

ArticleCancer cell international2026

Novel function of GTPBP2 in promoting hepatocellular carcinoma progression through inhibition of BTRC-mediated KRAS degradation.

Po-Shuan Huang, Hsiang-Cheng Chi, Yang-Hsiang Lin, Wei-Chieh Huang, Wan-Ting Liao, Pei-Yun Wang, Ling-Yu Wang, Yi-Wen Wang, Tzu-Kang Lin, Chia-Jung Liao and 5 more

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Article in Cancer cell international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Po-Shuan Huang *Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Hsiang-Cheng Chi *Institute of Biochemistry and Molecular Biology, China Medical University, Taichung, Taiwan.
Yang-Hsiang LinGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Wei-Chieh HuangChinese Medicine Research Center, China Medical University, Taichung, Taiwan.
Wan-Ting LiaoChinese Medicine Department, Show Chwan Memorial Hospital, Changhua, 500, Taiwan.
Pei-Yun WangDepartment of Nutrition, China Medical University, Taichung, Taiwan.
Ling-Yu WangDepartment of Biochemistry and Molecular Biology, Chang Gung University, Taoyuan, 333, Taiwan.
Yi-Wen WangSchool of Nursing, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Tzu-Kang LinNeurosurgery, Department of Surgery, Fu Jen Catholic University Hospital, New Taipei City, 24352, Taiwan.
Chia-Jung LiaoGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Che-Ju ChangGraduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
Ing-Shiow LayDepartment of Chinese Medicine, China Medical University Beigang Hospital, Yunlin, Taiwan.
Chau-Ting YehLiver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Lu-Hai WangChinese Medicine Research Center, China Medical University, Taichung, Taiwan. lu-hai.wang@nhri.edu.tw.
Kwang-Huei LinGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. khlin@mail.cgu.edu.tw.

Funding

Chiayi Chang Gung Memorial Hospital CMRPD1L0111, CMRPD1M0361~3China Medical University, Taiwan CMU110-IP-02, CMU111-MF-02 and CMU112-MF-04China Medical University, Taiwan CMU113-S-38National Science and Technology Council 110-2320-B-182-032, 111-2320-B-182-036National Science and Technology Council 112-2320-B-442 -001 and 113-2320-B-442 -001National Science and Technology Council 112-2326-B-039 -002 -MY3National Science and Technology Council 113-2811-B-039 -024, 113-2320-B-039 -001, 113-2634-F-039-001Show Chwan Memorial Hospital SRD-110051
6 · The paper itself

Abstract

backgroundDespite recent advancements in targeted therapies for hepatocellular carcinoma (HCC), therapeutic resistance continues to limit their clinical efficacy, highlighting an urgent need to identify novel molecular targets involved in disease progression and drug resistance.

methodsBoth gene set enrichment analysis (GSEA) and experimental gene expression analysis were employed to evaluate the role of GTPBP2 expression in HCC clinicopathogenesis using HCC tissue specimens and cell lines.

resultsIn this study, we reveal for the first time, the critical role of GTP-binding protein 2 (GTPBP2) as a key contributor to HCC progression and resistance to sorafenib treatment. Our findings demonstrate significant overexpression of GTPBP2 in HCC tissues compared to adjacent normal liver tissues, which strongly correlates with advanced tumor stage, increased tumor size, elevated alpha-fetoprotein (AFP) levels, enhanced sorafenib resistance, and poorer patient survival outcomes. Functional studies further confirm that GTPBP2 promotes aggressive tumor behaviors, including enhanced cell migration and invasion. Mechanistically, we uncover a novel function of GTPBP2 in stabilizing the KRAS oncoprotein by competitively binding βTrCP/BTRC, thus inhibiting KRAS ubiquitination and subsequent degradation. Consequently, this stabilization results in elevated activation of crucial downstream signaling pathways, such as p-AKT and p-MEK, which are implicated in tumor growth, metastasis, and drug resistance.

conclusionsCollectively, our study identifies GTPBP2 as a promising novel biomarker and therapeutic target, providing essential insights into HCC pathogenesis and offering new translational opportunities to overcome treatment resistance and improve patient outcomes.

Indexed as

BTRCGTPBP2HCCKRASMetastasisSorafenib resistance

Identifiers

PMID41634678
PMCPMC12955208

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.