ArticleProceedings of the National Academy of Sciences of the United States of America2010
The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis.
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 291 papers.
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Who cites it
291 citing papers in PubMed, 507 citations in OpenAlex.
- A Serum lncRNA Signature Determines Oncogenic YAP Activity in Cancer Patients.International journal of cancer · 2026Article
- ERK-Mediated Phosphorylation of YAP Defines a Noncanonical FGF Signaling Mechanism in Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- LATS kinase activity and tumor suppressor function are regulated by a second autophosphorylation site.The Journal of biological chemistry · 2026Article
- A Synergy between Genetics and Biochemistry Unravels the Molecular Architecture of the Hippo Signaling Pathway.Cold Spring Harbor perspectives in biology · 2026Article
- Oriented cell divisions induce basal progenitors and regulate neural expansion across tissues and species.Science advances · 2026Article
- The Patatin-Like Phospholipase Domain-Containing 3 148M Variant Exacerbates Alcohol-Induced Liver Injury and Tumorigenesis in Mice.The American journal of pathology · 2026Article
- A Bayesian pharmacokinetics integrated phase I-II design to optimize dose-schedule regimes.Biostatistics (Oxford, England) · 2025Article
- Taurochenodeoxycholic acid ameliorates liver fibrosis by regulating gut microbiota and bile acids via hippo-YAP pathway.iScience · 2025Article
- YAP-induced MAML1 cooperates with STAT3 to drive hepatocellular carcinoma progression.Experimental hematology & oncology · 2025Article
- Analysis of knockout mice reveals critical female-specific roles for the Hippo pathway component PTPN14.Genes & development · 2025Article
- Review
- Hyperactivated YAP1 is essential for sustainable progression of renal clear cell carcinoma.Oncogene · 2025Article
- The Hippo pathway effector YAP inhibits NF-κB signaling and ccRCC growth by opposing ZHX2.The Journal of biological chemistry · 2025Article
- Mammalian Ste20-like kinase 1 regulates AMPK to mitigate the progression of non-alcoholic fatty liver disease.European journal of medical research · 2025Article
- Morphomolecular Pathology and Genomic Insights into the Cells of Origin of Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma.The American journal of pathology · 2025Review
- HDAC4/MybL1/YAP novel signaling axis is required for pancreatic cancer metastasis to the liver.International journal of biological sciences · 2025Article
- Investigating the role of transforming growth factor-beta/transforming growth factor-beta receptor in the development of hepatocellular carcinoma through the Salvador-Warts-Hippo pathway.International journal of molecular and cellular medicine · 2025Article
- Cell competition drives bronchiolization and pulmonary fibrosis.Nature communications · 2024Article
- Whole-exome sequencing reveals genomic landscape of intrahepatic cholangiocarcinoma and identifies SAV1 as a potential driver.Nature communications · 2024Article
- Review
231 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 5 countries.
Funding
Abstract
Loss of Hippo signaling in Drosophila leads to tissue overgrowth as a result of increased cell proliferation and decreased cell death. YAP (a homolog of Drosophila Yorkie and target of the Hippo pathway) was recently implicated in control of organ size, epithelial tissue development, and tumorigenesis in mammals. However, the role of the mammalian Hippo pathway in such regulation has remained unclear. We now show that mice with liver-specific ablation of WW45 (a homolog of Drosophila Salvador and adaptor for the Hippo kinase) manifest increased liver size and expansion of hepatic progenitor cells (oval cells) and eventually develop hepatomas. Moreover, ablation of WW45 increased the abundance of YAP and induced its localization to the nucleus in oval cells, likely accounting for their increased proliferative capacity, but not in hepatocytes. Liver tumors that developed in mice heterozygous for WW45 deletion or with liver-specific WW45 ablation showed a mixed pathology combining characteristics of hepatocellular carcinoma and cholangiocarcinoma and seemed to originate from oval cells. Together, our results suggest that the mammalian Hippo-Salvador pathway restricts the proliferation of hepatic oval cells and thereby controls liver size and prevents the development of oval cell-derived tumors.
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Registered trials
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.