Evidence map›Paper›PMID 42020775›Full record

ArticleBritish journal of cancer2026

Inhibition of the SerpinB3/protease-activated receptor 2 axis reduces liver cancer development and affects lipid metabolism.

Pietro Guerra, Gianmarco Villano, Claudia M Rejano-Gordillo, Clàudia Gil-Pitarch, Mariagrazia Ruvoletto, Alessandra Biasiolo, Santina Quarta, L Estefanía Zapata-Pavas, Patricia Peña-SanFelix, Irene González-Recio and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2026. 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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

26 authors.

Pietro Guerra *Department of Medicine, University of Padova, Padova, Italy. pietro.guerra@phd.unipd.it.ORCID http://orcid.org/0009-0000-1288-709X
Gianmarco Villano *Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
Claudia M Rejano-GordilloLiver Disease and Liver Metabolism Laboratory, CIC bioGUNE-BRTA (Basque Research & Technology Alliance), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Spain.
Clàudia Gil-PitarchLiver Disease and Liver Metabolism Laboratory, CIC bioGUNE-BRTA (Basque Research & Technology Alliance), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Spain.
Mariagrazia RuvolettoDepartment of Medicine, University of Padova, Padova, Italy.
Alessandra BiasioloDepartment of Medicine, University of Padova, Padova, Italy.
Santina QuartaDepartment of Medicine, University of Padova, Padova, Italy.
L Estefanía Zapata-Pavas
Patricia Peña-SanFelixLiver Disease and Liver Metabolism Laboratory, CIC bioGUNE-BRTA (Basque Research & Technology Alliance), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Spain.
Irene González-RecioLiver Disease and Liver Metabolism Laboratory, CIC bioGUNE-BRTA (Basque Research & Technology Alliance), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Spain.
Naroa Goikoetxea-UsandizagaLiver Disease and Liver Metabolism Laboratory, CIC bioGUNE-BRTA (Basque Research & Technology Alliance), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Spain.
Jon Ander Barrenechea-BarrenecheaLiver Disease and Liver Metabolism Laboratory, CIC bioGUNE-BRTA (Basque Research & Technology Alliance), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Spain.
Arantza Sanz-ParraLiver Disease and Liver Metabolism Laboratory, CIC bioGUNE-BRTA (Basque Research & Technology Alliance), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Spain.
Alessandro GambellaPathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.
Silvia De SierviDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Barbara OlivieroDepartment of Translational and Clinical Research, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Stefania MantovaniDepartment of Translational and Clinical Research, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Jessica NurcisDepartment of Clinical and Biological Sciences, University of Torino, Turin, Italy.
Silvia CagninDepartment of Medicine, University of Padova, Padova, Italy.
Andrea MartiniDepartment of Medicine, Azienda Ospedale-Università of Padova, Padova, Italy.
Cristian TuratoDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Stefania CannitoDepartment of Clinical and Biological Sciences, University of Torino, Turin, Italy.
Maria GuidoDepartment of Medicine, University of Padova, Padova, Italy.
Maurizio ParolaDepartment of Clinical and Biological Sciences, University of Torino, Turin, Italy.
María Luz Martínez-ChantarLiver Disease and Liver Metabolism Laboratory, CIC bioGUNE-BRTA (Basque Research & Technology Alliance), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Spain. mlmartinez@cicbiogune.es.
Patrizia PontissoDepartment of Medicine, University of Padova, Padova, Italy.

Funding

Ministero della Salute (Ministry of Health, Italy) RF-2019-12369984
6 · The paper itself

Abstract

backgroundMASLD and HCC are increasing challenges in hepatology. 1-Piperidinepropionic acid (1-PPA), a protease-activated receptor 2 (PAR2) inhibitor, downregulates SerpinB3, a molecule involved in fibrosis and HCC. This study investigates the effects of 1-PPA on lipid accumulation and HCC development.

methods1-PPA was employed in primary hepatocytes and human liver organoids cultured with steatogenic compounds and lomitapide, a VLDL-formation inhibitor. Antitumoral effects of 1-PPA were evaluated by proliferation and invasion assays in HepG2 cells and in human liver organoids treated with a tumorigenic compound. MASH-related carcinogenesis was studied in vivo using C57BL/6J mice overexpressing SerpinB3 (C57/TG) and BALB/c mice deficient in the reactive site loop of Serpinb3a (BC/KO).

results1-PPA reduced tumour development and steatosis in vivo. Proteomic analysis showed decreased lipid synthesis and deposition post-treatment. Suppression of lipid accumulation was favoured by an increase in VLDL export, supported by an enhanced microsomal triglyceride transfer protein activity in vivo and by a competitive effect between 1-PPA and lomitapide in vitro. The compound 1-PPA also exhibited direct antitumoral effects, reducing proliferation, survival and invasion in liver organoids and HepG2 cells.

conclusions1-PPA administration prevents lipid accumulation and HCC development in MASH-related liver carcinogenesis.

Indexed as

Antigens, NeoplasmCarcinoma, HepatocellularLipid MetabolismLiver NeoplasmsPiperidinesSerpinsAnimalsCell ProliferationHepatocytesHep G2 CellsHumansMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutAntigens, NeoplasmPiperidinesSerpinssquamous cell carcinoma-related antigen

Identifiers

PMID42020775
PMCPMC13310849

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Registered trials

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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.