ArticleThe Journal of clinical investigation2017
Hippo signaling interactions with Wnt/β-catenin and Notch signaling repress liver tumorigenesis.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers.
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Who cites it
166 citing papers in PubMed, 239 citations in OpenAlex.
- Developing a strain-dependent susceptibility to hepatocellular carcinoma in a murine model based on histopathological evidence and genetic context.Animal models and experimental medicine · 2026Article
- Tumor Topography Remodels TME Signalling via Compartment-Specific Host-Microbiome-Tumor Crosstalk in Hepatoblastoma.Cancers · 2026Article
- The Hippo signaling pathway in pediatric brain tumors: molecular mechanisms and therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Mitogen-activated Protein Kinase big Mitogen-activated Kinase-1 Mediates Protection in Liver Ischemia/Reperfusion Injury.Transplantation · 2026Article
- Research on the Hippo Pathway in Cancer.Cells · 2026Review
- Hyperoxia-induced lung microvascular injury is mediated by endothelial cell-derived WNT5A.Journal of thoracic disease · 2026Article
- Celecoxib inhibits COX-2 and initiates YAP-dependent mitochondrial apoptosis via YBX1 shuttling in hepatocellular carcinoma.Cell communication and signaling : CCS · 2026Article
- Signalling pathways in hepatocellular carcinoma (HCC) metastasis and invasion: Molecular mechanisms and therapeutic implications.Biochemistry and biophysics reports · 2026Review
- YAP1 Is a Crucial Nexus in the Tumor Microenvironment.Current medical science · 2026Review
- CD160Cellular & molecular immunology · 2026Article
- Hepatocellular carcinoma-linkediScience · 2026Article
- Tumor-Derived Exosomal PDLIM1 Promotes Angiogenesis and Tumor Progression in Papillary Thyroid Carcinoma: Insights From Integrated Single-Cell Transcriptomics and Exosomal Proteomics.Cancer management and research · 2026Article
- On the mechanisms of epidermal stemness and differentiation.NPJ systems biology and applications · 2025Article
- Exosomes from liver progenitor cells carrying JAG1 activate notch signaling to promote liver regeneration in PVL rats.Cell death & disease · 2025Article
- YAP/TAZ: An epitome of tumorigenesis.Cancer letters · 2025Review
- Crosstalk between MST1-Hippo and Wnt/β-Catenin, Notch, and PI3K/Akt pathways in cardiac physiology and pathology.Journal of physiology and biochemistry · 2025Review
- Liver regeneration after partial hepatectomy: Triggers and mechanisms.World journal of hepatology · 2025Review
- Photothermal Hyperthermia Suppresses Liver Tumor Growth Via Hippo Signaling Pathway-Dependent Inhibition of Cell Proliferation and Induction of Apoptosis.Biological procedures online · 2025Article
- Spatial gene regulatory networks driving cell state transitions during human liver disease.EMBO molecular medicine · 2025Article
- Mechanisms of breast cancer metastasis: the role of extracellular matrix.Molecular and cellular biochemistry · 2025Review
106 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Malignant tumors develop through multiple steps of initiation and progression, and tumor initiation is of singular importance in tumor prevention, diagnosis, and treatment. However, the molecular mechanism whereby a signaling network of interacting pathways restrains proliferation in normal cells and prevents tumor initiation is still poorly understood. Here, we have reported that the Hippo, Wnt/β-catenin, and Notch pathways form an interacting network to maintain liver size and suppress hepatocellular carcinoma (HCC). Ablation of the mammalian Hippo kinases Mst1 and Mst2 in liver led to rapid HCC formation and activated Yes-associated protein/WW domain containing transcription regulator 1 (YAP/TAZ), STAT3, Wnt/β-catenin, and Notch signaling. Previous work has shown that abnormal activation of these downstream pathways can lead to HCC. Rigorous genetic experiments revealed that Notch signaling forms a positive feedback loop with the Hippo signaling effector YAP/TAZ to promote severe hepatomegaly and rapid HCC initiation and progression. Surprisingly, we found that Wnt/β-catenin signaling activation suppressed HCC formation by inhibiting the positive feedback loop between YAP/TAZ and Notch signaling. Furthermore, we found that STAT3 in hepatocytes is dispensable for HCC formation when mammalian sterile 20-like kinase 1 and 2 (Mst1 and Mst2) were removed. The molecular network we have identified provides insights into HCC molecular classifications and therapeutic developments for the treatment of liver tumors caused by distinct genetic mutations.
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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.