ArticleProceedings of the National Academy of Sciences of the United States of America2010
Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 444 papers.
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Who cites it
444 citing papers in PubMed, 719 citations in OpenAlex.
- Hippo Pathway-YAP/TAZ Signaling: Molecular Mechanisms, Biological Function, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Constitutive YAP activation in distal nephron segments disrupts epithelial identity and nephron patterning.JCI insight · 2026Article
- Sustained YAP/TAZ activation promotes aberrant alveolar epithelial cell differentiation and drives persistent fibrotic remodeling.JCI insight · 2026Article
- Enzymatic activity-independent NANS stabilizes LATS2 to drive growth and therapeutic resistance in HR+/HER2- breast cancer.Nature communications · 2026Article
- Recombinant bone morphogenetic protein-2 attenuates colorectal cancer progression by orchestrating Hippo pathway activation, Yes-associated protein inhibition, and epithelial-mesenchymal transition suppression.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- LATS kinase activity and tumor suppressor function are regulated by a second autophosphorylation site.The Journal of biological chemistry · 2026Article
- Plasma YAP1 as a biomarker for the prediction of occurrence, progression, and outcomes of sepsis-associated liver injury: a prospective observational study.BMC gastroenterology · 2026Observational
- A Synergy between Genetics and Biochemistry Unravels the Molecular Architecture of the Hippo Signaling Pathway.Cold Spring Harbor perspectives in biology · 2026Article
- USP25 aggravates liver cancer development and impairs chemosensitivity by limiting LATS1 activation.EMBO reports · 2026Article
- The Regulation and Function of Hippo/YAP Pathway in Cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- The Patatin-Like Phospholipase Domain-Containing 3 148M Variant Exacerbates Alcohol-Induced Liver Injury and Tumorigenesis in Mice.The American journal of pathology · 2026Article
- Dysadherin/YAP axis fuels stem plasticity and immune escape in liver cancer.Signal transduction and targeted therapy · 2025Article
- Constitutive Yap activation in distal nephron segments disrupts epithelial identity and nephron patterning.bioRxiv : the preprint server for biology · 2025Article
- YAP-induced MAML1 cooperates with STAT3 to drive hepatocellular carcinoma progression.Experimental hematology & oncology · 2025Article
- Lats1/2 Differentially Modulate the Proliferative State of Dental Epithelial Progenitors and Ameloblasts in the Murine Incisor.Orthodontics & craniofacial research · 2025Article
- Sodium taurocholate promotes liver regeneration after portal vein ligation in rats.Scientific reports · 2025Article
- Molecular mechanisms mediated by liquid-liquid phase separation in chronic liver disease progression.iScience · 2025Review
- The Ste20 Homologue FvM4K1 Regulates Organ Size via Hippo Signalling Pathway in Woodland Strawberry (Fragaria vesca).Plant biotechnology journal · 2025Article
- Oxytocin Receptor Regulates the Hippo/YAP Axis to Drive Hepatocarcinogenesis.Cancer research · 2025Article
- Analysis of knockout mice reveals critical female-specific roles for the Hippo pathway component PTPN14.Genes & development · 2025Article
384 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
How organ size is controlled in mammals is not currently understood. In Drosophila the Hippo signaling pathway functions to suppress growth in imaginal discs and has been suggested to control organ size. To investigate the role of hippo signaling in regulation of mammalian organ size we have generated conditional alleles of Sav1, mst1, and mst2, orthologs of Drosophila Salvador and hippo, respectively. Specific deletion of both mst1 and mst2 in hepatocytes results in significantly enlarged livers due to excessive proliferation. By the age of 5-6 months, mst1/2 conditional mutant livers have multiple foci of liver tumors, indicating that the combined activities of mst1 and mst2 act as redundant tumor suppressors in hepatocytes. Similar findings were obtained with liver-specific deletion of Sav1, a second core Hippo signaling component that facilitates activation of mst1 and mst2. Tumors from sav1 mutants exhibited varied morphology, suggesting a mixed-lineage origin of tumor-initiating cells. Transcriptional profiling of liver tissues from both mst1/2 and sav1 conditional mutants revealed a network of Hippo signaling regulated genes with specific enrichment for genes involved in immune and inflammatory responses. Histological and immunological characterization of mst1/2 double mutant liver tissues revealed abundant accumulation of adult facultative stem cells termed oval cells in periductal regions. Because oval cells induction is commonly associated with liver injury and tumor formation, it is likely that these cells contribute to the enlarged livers and hepatomas that we observe in sav1 and mst1/2 mutants. Taken together, our results demonstrate that the Hippo signaling pathway is a critical regulator of mammalian liver growth and a potent suppressor of liver tumor formation.
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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.