Evidence map›Paper›PMID 42612117›Full record

ArticleHepatology communications2026

Hepatic stellate cell subpopulations in human MASLD-related hepatocellular carcinoma upregulate YAP via geranylgeranyl pyrophosphate.

Courtney L Labrecque, Arthur Ko, Bo Qiao, Calvin Pan, Renu Nandakumar, Kushan Chowdhury, Namrata Venkatesan, Xiaotang Du, Bishuang Cai, Matteo Pellegrini and 6 more

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In one paragraph

Article in Hepatology communications, 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

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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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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

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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

16 authors.

Courtney L LabrecqueVeterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.ORCID 0000-0002-6075-853
Arthur KoCenter for Precision Medicine and Genomic Research, Children's National Research Institute, Washington, District of Columbia, USA.
Bo QiaoVeterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.
Calvin PanDavid Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Renu NandakumarColumbia University Biomarkers Core Laboratory, New York, New York, USA.
Kushan ChowdhuryDavid Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Namrata VenkatesanVeterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.
Xiaotang DuDepartment of Pathology, University of California Los Angeles, Los Angeles, California, USA.
Bishuang CaiDavid Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Matteo PellegriniComprehensive Liver Research Center, University of California, Los Angeles, California, USA.
Joseph R PisegnaVeterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.
Samuel W FrenchComprehensive Liver Research Center, University of California, Los Angeles, California, USA.
Vatche AgopianComprehensive Liver Research Center, University of California, Los Angeles, California, USA.
Enrique RozengurtDavid Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Rajat SinghDavid Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Jihane N BenhammouVeterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.

Funding

EHD1-mediated Inflammation and Resolution in AtherosclerosisR01HL167107 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Bishuang Cai · 2023 to 2026
$2.8M
Efferocytosis meets endocytosisR35GM147269 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Bishuang Cai · 2022 to 2026
$2.3M
Disturbed Crosstalk between Cholesterol Homeostasis and Inflammation Resolution in NASHR01DK134610 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Bishuang Cai · 2023 to 2026
$2.2M
CSRD VA IK2 CX002593NHLBI NIH HHS R01 HL167107NIDDK NIH HHS R01 DK134610NIGMS NIH HHS R35 GM147269
6 · The paper itself

Abstract

backgroundHepatic stellate cells (HSCs) drive cirrhosis and hepatocellular carcinoma (HCC). Statin use decreases cirrhosis and HCC through unclear mechanisms. We aimed to uncover statin-responsive pathways preventing activation of HSC subpopulations in human MASLD-HCC.

methodsWe used single-nucleus RNA-sequencing and spatial imaging on matched human MASLD-HCC samples in cirrhotic and non-cirrhotic livers, along with RNA-sequencing of human primary HSCs to identify Yes-Associated Protein (YAP) as a statin-responsive pathway, which was assessed for cellular localization and function, that is, downstream gene expression after statin exposure. We used pharmacologic inhibitors, gene silencing, pharmacological repletion, and direct quantification by UPLC-MS/MS to interrogate the mevalonate pathway as a statin-responsive YAP regulator.

resultsWe identified an HCC-HSC subcluster enriched in activated and deactivated marker genes. Spatial resolution of each cell type revealed that myofibroblast-like HSC subpopulations and YAP-effector genes colocalized in the peritumoral pseudocapsule. In fact, although Rho GTPases were differentially expressed across most cell types, YAP-effector genes were largely upregulated in HCC-HSCs by single-nucleus RNA sequencing. Bulk RNA-sequencing of statin-treated activated human primary HSCs showed decreased expression of YAP-related genes and downregulation of Rho GTPase pathways in response to statins. Statins reduced GGPP levels in LX2 HSCs, determined by direct measurement of intracellular GGPP, which was associated with cytoskeletal restructuring, YAP cytosolic retention, and reduced YAP-effector gene expression. Exogenous GGPP repletion reversed these effects. GGPP synthase 1 knockdown and direct Rho inhibition recapitulated the cellular responses of YAP following statin exposure.

conclusionsUpregulation of YAP-effector genes was largely restricted to HCC-HSCs. Our mechanistic studies support that statins lower GGPP, reduce Rho GTPases prenylation, cause YAP cytosolic retention, and decrease YAP nuclear activity. This study expands on the chemoprotective mechanisms of statins in HCC.

Indexed as

Adaptor Proteins, Signal TransducingCarcinoma, HepatocellularHepatic Stellate CellsLiver NeoplasmsPolyisoprenyl PhosphatesTranscription FactorsHumansHydroxymethylglutaryl-CoA Reductase InhibitorsLiver CirrhosisUp-RegulationYAP-Signaling ProteinsAdaptor Proteins, Signal Transducinggeranylgeranyl pyrophosphateHydroxymethylglutaryl-CoA Reductase InhibitorsPolyisoprenyl PhosphatesTranscription FactorsYAP1 protein, humanYAP-Signaling Proteinsgeranylgeranyl pyrophosphatehepatocellular carcinomaRho GTPasessingle-nucleus RNA sequencingspatial imagingstatinsyes-associated protein

Identifiers

PMID42612117
PMCPMC13480919

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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.