Evidence map›Paper›PMID 42092696›Full record

ArticleCellular and molecular gastroenterology and hepatology2026

Vacuolar Protein Sorting 35 Controls Hepatocellular Proliferation Through SRC Signaling and Promotes Diethyl Nitrosamine-Induced Tumor Initiation.

Markus G Barbosa, Dyonne Y Vos, Cristy R C Verzijl, Andries H Heida, Marco Bakker, Niels J Kloosterhuis, Mirjam H Koster, Marieke Smit, Alba Fajardo, Dicky Struik and 9 more

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Article in Cellular and molecular gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

19 authors.

Markus G BarbosaDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Dyonne Y VosDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Cristy R C VerzijlDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Andries H HeidaDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Marco BakkerDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Niels J KloosterhuisDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Mirjam H KosterDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Marieke SmitDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Alba FajardoLipid Trafficking and Disease Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
Dicky StruikDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Peter OlingaDepartment of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands.
Johan W JonkerDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Rachel ThomasDepartment of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Albert PolLipid Trafficking and Disease Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Vincent E de MeijerDepartment of of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Anna MolesInstitut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; Department of Experimental Pathology, Institute of Biomedical Research of Barcelona, Spanish National Research Council (CSIC), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
Umesh TharehalliDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Jan Albert KuivenhovenDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Bart van de SluisDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: a.j.a.van.de.sluis@umcg.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsHepatocellular carcinoma is the third leading cause of cancer-related mortality worldwide. Therapeutic options for hepatocellular carcinoma remain limited, and the mechanisms underlying hepatocellular carcinoma are not fully understood. Therefore, gaining a comprehensive understanding of the pathways that drive hepatocellular carcinoma is essential for improving treatments. Recent studies have identified vacuolar protein sorting 35, a component of the endosomal cargo sorting machinery called retromer, as a novel oncogene in various types of cancer, including hepatocellular carcinoma. However, its role in the initiation and progression of hepatocellular carcinoma is still unclear.

methodsTo study the role of vacuolar protein sorting 35 in hepatocellular proliferation and the development of hepatocellular carcinoma, we generated a liver-specific Vps35 knockout mouse model using the Cre-LoxP system (Vps35

resultsHepatic loss of vacuolar protein sorting 35 enhanced hepatocellular proliferation in post-natal livers via SRC and its downstream target signal transducer and activator of transcription 3. Pharmacologic inhibition of SRC with saracatinib normalized hepatocellular proliferation in Vps35

conclusionsOur in vivo data identify murine vacuolar protein sorting 35 as a critical regulator of hepatocellular proliferation in postnatal livers, but not after partial hepatectomy. Although vacuolar protein sorting 35 deficiency mitigates diethyl nitrosamine-induced liver lesion formation, it does not affect tumor progression, arguing against a role for vacuolar protein sorting 35 as a canonical oncogene.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsVesicular Transport ProteinsAnimalsCell ProliferationDiethylnitrosamineDisease Models, AnimalHumansLiverLiver RegenerationMaleMiceMice, KnockoutSignal TransductionDiethylnitrosamineVesicular Transport ProteinsEndosomal TransportLiver CancerLiver DevelopmentOncogene

Identifiers

PMID42092696
PMCPMC13310651

What Socratic holds

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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 Socratic graph.