ArticleCell metabolism2019
Inhibiting Glutamine-Dependent mTORC1 Activation Ameliorates Liver Cancers Driven by β-Catenin Mutations.
Open access · bronzeAbstract read
In one paragraph
Article in Cell metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed
6.0field-weighted citation impact, top 3% of its field
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.
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.
Who cites it
95 citing papers in PubMed, 162 citations in OpenAlex.
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Multi-Omics-Guided Design and Safety Engineering of Nucleic Acid Therapeutics: From Molecular Perturbation to Predictive Toxicology and Precision Translation.Chemical biology & drug design · 2026Review
- Targeting the 4EBP1/HSP90β/Nrf2 Axis Sensitizes β-catenin-mutant Hepatocellular Carcinoma to mTOR Inhibitors via Ferroptosis Induction.Journal of clinical and translational hepatology · 2026Article
- Targeting ferroptosis induction via nanomaterials in hepatocellular carcinoma: an insight into mechanism and therapeutic potential.Journal of nanobiotechnology · 2026Review
- Crosstalk BetweenCancers · 2026Review
- WNT-β-catenin signalling in hepatocellular carcinoma: from bench to clinical trials.Nature reviews. Gastroenterology & hepatology · 2026Review
- The origin of hepatocellular carcinoma depends on metabolic zonation.Science (New York, N.Y.) · 2026Article
- Amino acid metabolic reprogramming: future prospects for cholangiocarcinoma therapy.Cell death discovery · 2026Review
- Metabolic characteristics in hepatocellular carcinoma: amino acid metabolic reprogramming.Molecular cancer · 2026Review
- Metabolic Reprogramming-Targeted Therapeutic Strategies in Primary Liver Cancer: A Bibliometric and Visualized Analysis.Journal of hepatocellular carcinoma · 2026Article
- New understanding of the molecular pathogenesis and therapeutic progress of hepatocellular carcinoma.Oncology reviews · 2026Review
- Ammonia reduces glutamine synthetase expression in astrocytes via activation of Hippo-YAP signaling pathways.Communications biology · 2025Article
- Precision targeting of β-catenin induces tumor reprogramming and immunity in hepatocellular cancers.Nature communications · 2025Article
- Engineered nanoparticles for imaging and targeted drug delivery in hepatocellular carcinoma.Experimental hematology & oncology · 2025Review
- New insights into biomarkers and risk stratification to predict hepatocellular cancer.Molecular medicine (Cambridge, Mass.) · 2025Review
- Metabolic reprogramming in hepatocellular carcinoma: mechanisms and therapeutic implications.Experimental & molecular medicine · 2025Review
- Precision models in hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2025Review
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Transcriptomic analysis of Paraoxonase 1 expression in hepatocellular carcinoma and its potential impact on tumor immunity.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Toxin protein LukS-PV targeting complement receptor C5aR1 inhibits cell proliferation in hepatocellular carcinoma via the HDAC7-Wnt/β-catenin axis.The Journal of biological chemistry · 2025Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
25 authors at 7 institutions in 4 countries.
Adeola O Adebayo MichaelDivision of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Sungjin KoDivision of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Junyan TaoDivision of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Akshata MoghePittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Hong YangDivision of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Meng XuDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, PR China; Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, San Francisco, CA, USA.
Jacquelyn O RussellDivision of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Tirthadipa Pradhan-SunddDivision of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Silvia LiuDivision of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Sucha SinghDivision of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Minakshi PoddarDivision of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Jayvir S MongaDivision of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Pin LiuDepartment of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, PR China.
Michael OertelDivision of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Sarangarajan RanganathanPittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Division of Pediatric Pathology, Department of Pathology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Aatur SinghiPittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Division of Anatomic Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Sandra RebouissouInserm, UMR-1162, Génomique fonctionnelle des Tumeurs solides, Equipe Labellisée Ligue Contre le Cancer, Paris 75010, France; Université Paris Descartes, Labex Immuno-Oncology, Sorbonne Paris Cité, 75010 Paris, France; Université Paris 13, Sorbonne Paris Cité, UFR SMBH, 93000 Bobigny, France; Université Paris Diderot, IUH, 75010 Paris, France.
Jessica Zucman-RossiInserm, UMR-1162, Génomique fonctionnelle des Tumeurs solides, Equipe Labellisée Ligue Contre le Cancer, Paris 75010, France; Université Paris Descartes, Labex Immuno-Oncology, Sorbonne Paris Cité, 75010 Paris, France; Université Paris 13, Sorbonne Paris Cité, UFR SMBH, 93000 Bobigny, France; Université Paris Diderot, IUH, 75010 Paris, France.
Silvia RibbackInstitute of Pathology, University of Greifswald, Greifswald, Germany.
Diego CalvisiInstitute of Pathology, University of Greifswald, Greifswald, Germany.
Natalia QvartskhavaClinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Boris GörgClinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Dieter HäussingerClinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Xin ChenDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, San Francisco, CA, USA.
Satdarshan P MongaDivision of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: smonga@pitt.edu.
University of Pittsburgh · USHeinrich Heine University Düsseldorf · DEDélégation Paris 5 · FRUniversität Greifswald · DEUniversity of California, San Francisco · USGuangxi Medical University · CNWuhan University · CN
Funding
Role of Wnt/Beta-Catenin Signaling in Liver DevelopmentR01DK062277 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Satdarshan Singh Monga · 2004 to 2026
$9.0MElucidating the role of the FXR-PTEN-PI3K-AKT-mTOR axis in liver progenitor cell-driven liver regenerationR01DK101426 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHIN, DONGHUN · 2014 to 2023
$3.8MTranslational Research Training in Cancer Prevention and ControlT32CA186873 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Kathryn H. Schmitz, Jian-Min Yuan · 2014 to 2026
$2.7MMolecular Genetics of Liver CancersR01CA136606 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHEN, XIN · 2009 to 2016
$2.6MMapping Disease Pathways for Biliary AtresiaR01DK109365 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHIN, DONGHUN, SINDHI, RAKESH K. · 2017 to 2020
$2.4MDelineating Molecular Mechanisms Underlying Liver Progenitor Cell-Driven Liver RegenerationR01DK116993 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MONGA, SATDARSHAN SINGH, SHIN, DONGHUN · 2018 to 2021
$2.2MYap and beta-catenin interactions in liver: Implications in PathophysiologyR01CA204586 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, XIN, MONGA, SATDARSHAN SINGH · 2016 to 2020
$2.1MTargeting beta-catenin in liver pathology: Novel Interactions, Novel ParadigmsR01DK100287 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MONGA, SATDARSHAN SINGH · 2013 to 2016
$1.3MNCI NIH HHS R01 CA136606NCI NIH HHS R01 CA204586NCI NIH HHS T32 CA186873NIDDK NIH HHS R01 DK062277NIDDK NIH HHS R01 DK100287NIDDK NIH HHS R01 DK101426NIDDK NIH HHS R01 DK109365NIDDK NIH HHS R01 DK116993
Abstract
Based on their lobule location, hepatocytes display differential gene expression, including pericentral hepatocytes that surround the central vein, which are marked by Wnt-β-catenin signaling. Activating β-catenin mutations occur in a variety of liver tumors, including hepatocellular carcinoma (HCC), but no specific therapies are available to treat these tumor subsets. Here, we identify a positive relationship between β-catenin activation, its transcriptional target glutamine synthetase (GS), and p-mTOR-S2448, an indicator of mTORC1 activation. In normal livers of mice and humans, pericentral hepatocytes were simultaneously GS and p-mTOR-S2448 positive, as were β-catenin-mutated liver tumors. Genetic disruption of β-catenin signaling or GS prevented p-mTOR-S2448 expression, while its forced expression in β-catenin-deficient livers led to ectopic p-mTOR-S2448 expression. Further, we found notable therapeutic benefit of mTORC1 inhibition in mutant-β-catenin-driven HCC through suppression of cell proliferation and survival. Thus, mTORC1 inhibitors could be highly relevant in the treatment of liver tumors that are β-catenin mutated and GS positive.
Indexed as
MutationAcetatesAnimalsbeta CateninCarcinoma, HepatocellularCell Line, TumorCell ProliferationCell SurvivalChildChild, PreschoolDisease Models, AnimalFemaleGlutamate-Ammonia LigaseGlutamineHepatocytesHumansAcetatesbeta CateninCTNNB1 protein, humanCTNNB1 protein, mouseGC 1 compoundGlutamate-Ammonia LigaseGlutamineMechanistic Target of Rapamycin Complex 1MTOR protein, humanPhenolsSirolimusTOR Serine-Threonine Kinasesbeta-cateninglutamine synthetasehepatocellular cancerliver tumormetabolic zonationmTORpersonalized medicineprecision therapytumor metabolismWnt
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.