Evidence map›Paper›PMID 41467954›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2025

SERPINA1 drives TACE resistance in hepatocellular carcinoma by competitively binding ITGB3 to block ITCH-mediated ubiquitination and degradation.

Liou Zhang, Xiaoxi Bai, Mingyang Du, Wenyue Dou, Ziwen Xie, Jie Liu, Yang Hou

Abstract read
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Liou Zhang *Department of Interventional Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.ORCID http://orcid.org/0009-0009-8666-7861
Xiaoxi Bai *Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
Mingyang Du *Department of Interventional Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
Wenyue DouDepartment of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
Ziwen XieDepartment of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
Jie LiuTranslational Research Experiment Department, Science Experiment Center, China Medical University, Shenyang, Liaoning Province, 110122, China. jieliu@cmu.edu.cn.
Yang HouDepartment of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China. houyang1973@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTransarterial chemoembolization (TACE) is the first-line treatment for intermediate-to-advanced hepatocellular carcinoma (HCC), but post-TACE resistance remains a major clinical challenge. While SERPINA1, a serine protease inhibitor involved in tumor microenvironment regulation, is dysregulated in various cancers, its role in TACE resistance is unclear. This study investigates SERPINA1’s functional and mechanistic involvement in HCC resistance to TACE.

methodsSerum SERPINA1 levels were measured by ELISA in TACE-treated HCC patients. Functional assays under hypoxic/chemotherapeutic conditions and xenograft models assessed tumor progression. Mechanistic studies integrated qRT-PCR, Western blot, co-immunoprecipitation (Co-IP), GST pull-down, molecular docking, and mass spectrometry to elucidate the SERPINA1-ITGB3 interaction.

resultsElevated post-TACE serum SERPINA1 levels were significantly associated with poor treatment response and poor prognosis (P < 0.05). Functional experiments demonstrated that SERPINA1 promoted HCC cell proliferation, migration, and invasion under hypoxic and chemotherapeutic stress, while xenograft models confirmed its tumorigenic role. Mechanistically, SERPINA1 competitively bound to the EGF-like 2/3 domains of ITGB3 via its C-terminal region (amino acids 320–392), thereby shielding ITGB3 from ITCH-mediated polyubiquitination and proteasomal degradation, which consequently sustained oncogenic signaling pathways.

conclusionOur study identifies the SERPINA1-ITGB3 axis as a critical mediator of TACE resistance in HCC, providing a promising therapeutic target to enhance clinical outcomes.

Indexed as

alpha 1-AntitrypsinCarcinoma, HepatocellularChemoembolization, TherapeuticDrug Resistance, NeoplasmIntegrin beta3Liver NeoplasmsProteolysisAnimalsCell Line, TumorCell MovementCell ProliferationFemaleHumansMaleMiceMice, Inbred BALB Calpha 1-AntitrypsinIntegrin beta3SERPINA1 protein, humanHepatocellular carcinomaITGB3SERPINA1Transarterial chemoembolizationUbiquitination

Identifiers

PMID41467954
PMCPMC12753576

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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.