ArticlePLoS biology2019
The Hippo pathway integrates PI3K-Akt signals with mechanical and polarity cues to control tissue growth.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 133 citations in OpenAlex.
- A tumour-host feed-forward loop contributes to the growth of chromosomal instability-induced tumours.EMBO reports · 2026Article
- Impact of somatic PIK3CA mutations on clinical outcomes in HER2-positive breast cancer.Breast cancer research : BCR · 2026Article
- Mechanobiology of the Hippo-YAP Signaling Network.Cold Spring Harbor perspectives in biology · 2026Article
- Hippo-YAP/TAZ Signaling in Astrocytes and Microglia: Role in Neuroinflammation, Neurodegeneration and Glial Tumors.International journal of molecular sciences · 2026Review
- The Regulation and Function of Hippo/YAP Pathway in Cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
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- PRIP/PLCL deficiency activates PI3K-AKT-YAP signaling and promotes organ fibrosis.Cell communication and signaling : CCS · 2026Article
- The Evolutionarily Conserved TPM1 Super-Enhancer Drives Skeletal Muscle Regeneration via Mechanotransduction Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Functional nucleic acid Hydrogels: Paving the way for Next-generation bone and cartilage regeneration.Materials today. Bio · 2026Review
- Transcriptome analysis of perforated small cocoon from Bombyx mori mutants.Scientific reports · 2026Article
- Surface mechanics and compressive stress impact mammalian follicle development.Nature communications · 2025Article
- Article
- Hippo Signaling Dysregulation in Breast Cancer: Subtype-Independent Gene and miRNA Signatures.Biomedicines · 2025Article
- Targeting developmental vulnerabilities in childhood sarcomas.Cancer metastasis reviews · 2025Review
- Review
- Effect of whole-plant mulberry supplementation on testis development and antioxidant capacity in Hu rams.Animal bioscience · 2025Article
- Hippo Pathway Dysregulation in Thymic Epithelial Tumors (TETs): Associations with Clinicopathological Features and Patients' Prognosis.International journal of molecular sciences · 2025Article
- Effects of melatonin in polycystic ovary syndrome: is there Hippo pathway crosstalk?Journal of ovarian research · 2025Review
- Oncogenic signaling in the Drosophila prostate-like accessory gland activates a pro-tumorigenic program in the absence of proliferation.Disease models & mechanisms · 2025Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Hippo signalling pathway restricts cell proliferation in animal tissues by inhibiting Yes-associated protein (YAP or YAP1) and Transcriptional Activator with a PDZ domain (TAZ or WW-domain-containing transcriptional activator [WWTR1]), coactivators of the Scalloped (Sd or TEAD) DNA-binding transcription factor. Drosophila has a single YAP/TAZ homolog named Yorkie (Yki) that is regulated by Hippo pathway signalling in response to epithelial polarity and tissue mechanics during development. Here, we show that Yki translocates to the nucleus to drive Sd-mediated cell proliferation in the ovarian follicle cell epithelium in response to mechanical stretching caused by the growth of the germline. Importantly, mechanically induced Yki nuclear localisation also requires nutritionally induced insulin/insulin-like growth factor 1 (IGF-1) signalling (IIS) via phosphatidyl inositol-3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1 or PDPK1), and protein kinase B (Akt or PKB) in the follicular epithelium. We find similar results in the developing Drosophila wing, where Yki becomes nuclear in the mechanically stretched cells of the wing pouch during larval feeding, which induces IIS, but translocates to the cytoplasm upon cessation of feeding in the third instar stage. Inactivating Akt prevents nuclear Yki localisation in the wing disc, while ectopic activation of the insulin receptor, PI3K, or Akt/PKB is sufficient to maintain nuclear Yki in mechanically stimulated cells of the wing pouch even after feeding ceases. Finally, IIS also promotes YAP nuclear localisation in response to mechanical cues in mammalian skin epithelia. Thus, the Hippo pathway has a physiological function as an integrator of epithelial cell polarity, tissue mechanics, and nutritional cues to control cell proliferation and tissue growth in both Drosophila and mammals.
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