ArticleThe EMBO journal2023
Two Hippo signaling modules orchestrate liver size and tumorigenesis.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
- YAP/TEAD complex restricts H3K27ac deposition to suppress testosterone synthesis in adult Leydig cells.Histochemistry and cell biology · 2026Article
- LATS kinase activity and tumor suppressor function are regulated by a second autophosphorylation site.The Journal of biological chemistry · 2026Article
- Regulation of STK38 by autophagy governs YAP1 activity during paligenosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- WWC proteins as emerging biomarkers and therapeutic targets in cancer pathogenesis.Frontiers in cell and developmental biology · 2026Review
- Proteasome stress activates YAP/TAZ through the RAP2-MAP4Ks-LATS1/2 pathway and its therapeutic implications in solid tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Analysis of knockout mice reveals critical female-specific roles for the Hippo pathway component PTPN14.Genes & development · 2025Article
- Research and development prospects of TRIM65.Journal of cancer research and clinical oncology · 2025Review
- Estrogen receptor α suppresses hepatocellular carcinoma by restricting M2 macrophage infiltration through the YAP-CCL2 axis.BMC cancer · 2025Article
- 5-Methylcytosine Methylation-Linked Hippo Pathway Molecular Interactions Regulate Lipid Metabolism.International journal of molecular sciences · 2025Review
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- WWC proteins-mediated compensatory mechanism restricts schwannomatosis driven byScience advances · 2025Article
- YAP/TAZ-associated cell signaling - at the crossroads of cancer and neurodevelopmental disorders.Frontiers in cell and developmental biology · 2025Review
- Hippo/YAP signaling pathway in colorectal cancer: regulatory mechanisms and potential drug exploration.Frontiers in oncology · 2025Review
- Hippo signaling pathway in polycystic ovary syndrome.Frontiers in endocrinology · 2025Review
- PRMT1-mediated arginine methylation promotes YAP activation and hepatocellular carcinoma proliferation.FEBS open bio · 2024Article
- TRIM65/NF2/YAP1 Signaling Coordinately Orchestrates Metabolic and Immune Advantages in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Circular RNA circ_ARHGEF28 inhibits MST1/2 dimerization to suppress Hippo pathway to induce cisplatin resistance in ovarian cancer.Cancer cell international · 2024Article
- NF2: An underestimated player in cancer metabolic reprogramming and tumor immunity.NPJ precision oncology · 2024Review
- CCDC25 suppresses clear cell renal cell carcinoma progression by LATS1/YAP-mediated regulation of the hippo pathway.Cancer cell international · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Hippo pathway is a central regulator of organ size and tumorigenesis and is commonly depicted as a kinase cascade, with an increasing number of regulatory and adaptor proteins linked to its regulation over recent years. Here, we propose that two Hippo signaling modules, MST1/2-SAV1-WWC1-3 (HPO1) and MAP4K1-7-NF2 (HPO2), together regulate the activity of LATS1/2 kinases and YAP/TAZ transcriptional co-activators. In mouse livers, the genetic inactivation of either HPO1 or HPO2 module results in partial activation of YAP/TAZ, bile duct hyperplasia, and hepatocellular carcinoma (HCC). On the contrary, inactivation of both HPO1 and HPO2 modules results in full activation of YAP/TAZ, rapid development of intrahepatic cholangiocarcinoma (iCCA), and early lethality. Interestingly, HPO1 has a predominant role in regulating organ size. HPO1 inactivation causes a homogenous YAP/TAZ activation and cell proliferation across the whole liver, resulting in a proportional and rapid increase in liver size. Thus, this study has reconstructed the order of the Hippo signaling network and suggests that LATS1/2 and YAP/TAZ activities are finetuned by HPO1 and HPO2 modules to cause different cell fates, organ size changes, and tumorigenesis trajectories.
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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.