The Hippo pathway: regulators and regulations.
Open accessAbstract
Control of cell number is crucial in animal development and tissue homeostasis, and its dysregulation may result in tumor formation or organ degeneration. The Hippo pathway in both Drosophila and mammals regulates cell number by modulating cell proliferation, cell death, and cell differentiation. Recently, numerous upstream components involved in the Hippo pathway have been identified, such as cell polarity, mechanotransduction, and G-protein-coupled receptor (GPCR) signaling. Actin cytoskeleton or cellular tension appears to be the master mediator that integrates and transmits upstream signals to the core Hippo signaling cascade. Here, we review regulatory mechanisms of the Hippo pathway and discuss potential implications involved in different physiological and pathological conditions.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Ndr kinases are conserved from yeast to human and act as components of an essential pathway.
“The nuclear Dbf2-related (Ndr) kinases act as components of one of these essential pathways and are conserved from yeast to human (Hergovich et al., 2006b; Yu and Guan, 2013).”
From Rassf5 and Ndr kinases act in a novel pathway regulating neuronal polarity through Par3 phosphorylation (2014) · cites this paper as Yu and Guan, 2013
The passage describing the core Hippo pathway (indexed under Abstract; page unavailable) identifies Lats1/2 as components of a kinase cascade conserved between Drosophila and mammals. It does not identify them as Ndr kinases or establish conservation from yeast to humans, and it does not call the pathway essential. (LLM, conf=0.78)
Experimental — accuracy not yet measuredMammalian Ndr1 and Ndr2 share a conserved kinase domain with Drosophila Warts and mammalian Lats1 and Lats2.
“Mammalian Ndr1 (also known as STK38) and Ndr2 (also known as STK38L) share a conserved kinase domain with Drosophila Warts and mammalian Large tumor suppressor (Lats) 1 and 2 (Hergovich et al., 2006a; Hergovich et al., 2006b; Yu and Guan, 2013).”
From Rassf5 and Ndr kinases act in a novel pathway regulating neuronal polarity through Par3 phosphorylation (2014) · cites this paper as Yu and Guan, 2013
The paper identifies mammalian Lats1/2 as orthologs of Drosophila Warts in its Hippo-pathway discussion and Table 1 (page unavailable). It does not state that Ndr1 or Ndr2 shares a conserved kinase domain with them; searches for Ndr1 and NDR kinase domain found no supporting passage. (LLM, conf=0.81)
Experimental — accuracy not yet measuredTEAD2 functions as a nuclear transcription factor in the Hippo signaling pathway, which can regulate cell death, proliferation, and differentiation.
“TEAD2 functions as a nuclear TF in the Hippo signaling pathway, which can regulate cell death, proliferation, and differentiation (reviewed in Yu and Guan, 2013).”
From Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation (2014) · cites this paper as Yu and Guan, 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Role of YAP/TAZ in mechanotransduction
Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S., et al. (2011) · Nature · doi:10.1038/nature10137 · Cited by 5,979 · see citing works
Local force and geometry sensing regulate cell functions
Vogel, V., & Sheetz, M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1890 · Cited by 2,328 · cited 2× · see citing works
“Cells are able to sense and adapt to these mechanical signals and may undergo proliferation, differentiation, apoptosis, and migration (Vogel and Sheetz 2006).”
BackgroundRegulation of the Hippo-YAP Pathway by G-Protein-Coupled Receptor Signaling
Yu, F.-X., Zhao, B., Panupinthu, N., Jewell, J. L., Lian, I., Wang, L. H., Zhao, J., Yuan, H., Tumaneng, K., Li, H., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.037 · Cited by 1,628 · see citing works
Self-citationWu, S., Liu, Y., Zheng, Y., Dong, J., & Pan, D. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.01.007 · Cited by 640 · see citing works
PTPN14 is required for the density-dependent control of YAP1
Wang, W., Huang, J., Wang, X., Yuan, J., Li, X., Feng, L., Park, J.-I., & Chen, J. (2012) · Genes & Development · doi:10.1101/gad.192955.112 · Cited by 195 · see citing works
Judson, R. N., Tremblay, A. M., Knopp, P., White, R. B., Urcia, R., De Bari, C., Zammit, P. S., Camargo, F. D., & Wackerhage, H. (2012) · Journal of Cell Science · doi:10.1242/jcs.109546 · Cited by 190 · see citing works
Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development
Skouloudaki, K., Puetz, M., Simons, M., Courbard, J.-R., Boehlke, C., Hartleben, B., Engel, C., Moeller, M. J., Englert, C., Bollig, F., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811691106 · Cited by 163 · see citing works
Zecca, M., & Struhl, G. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000386 · Cited by 148 · see citing works
Yap is a novel regulator of C2C12 myogenesis
Watt, K. I., Judson, R., Medlow, P., Reid, K., Kurth, T. B., Burniston, J. G., Ratkevicius, A., Bari, C. D., & Wackerhage, H. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.02.034 · Cited by 144 · see citing works
Nguyen, H. B., Babcock, J. T., Wells, C. D., & Quilliam, L. A. (2013) · Oncogene · doi:10.1038/onc.2012.431 · Cited by 84 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- Huang JM, Nagatomo I, Suzuki E, Mizuno T, Kumagai T, Berezov A, Zhang H, Karlan B, Greene MI, Wang Q. 2012. YAP modifies cancer cell sensitivity to EGFR and survivin inhibitors and is negatively regulated by the non-receptor type protein tyrosine phosphatase 14. Oncogene doi: 10.1038/ onc.2012.231. · DOI
- Liu X, Yang N, Figel SA, Wilson KE, Morrison CD, Gelman IH, Zhang J. 2012. PTPN14 interacts with and negatively regu- lates the oncogenic function of YAP. Oncogene doi: 10.1038/ onc.2012.147. · DOI · Paper page
- Tagliabracci VS, Engel JL, Wen J, Wiley SE, Worby CA, Kinch LN, Xiao J, Grishin NV, Dixon JE. 2012. Secreted kinase phosphorylates extracellular proteins that regulate biomin- eralization. Science 336: 1150-1153.
- Wehr MC, Holder MV, Gailite I, Saunders RE, Maile TM, Ciirdaeva E, Instrell R, Jiang M, Howell M, Rossner MJ, et al. 2012. Salt-inducible kinases regulate growth through the Hippo signalling pathway in Drosophila. Nat Cell Biol (in press). doi: 10.1038/ncb2658. · DOI
Cited by
Sorted by citations
Hippo pathway in organ size control, tissue homeostasis, and cancer
Yu, F.-X., Zhao, B., & Guan, K.-L. (2015) · Cell · doi:10.1016/j.cell.2015.10.044 · Cited by 2,206 · see citing works
Self-citationMechanisms of Hippo pathway regulation
Meng, Z., Moroishi, T., & Guan, K.-L. (2016) · Genes & Development · doi:10.1101/gad.274027.115 · Cited by 1,667 · see citing works
Self-citationA gp130–Src–YAP module links inflammation to epithelial regeneration
Taniguchi, K., Wu, L.-W., Grivennikov, S. I., de Jong, P. R., Lian, I., Yu, F.-X., Wang, K., Ho, S. B., Boland, B. S., Chang, J. T., et al. (2015) · Nature · doi:10.1038/nature14228 · Cited by 633 · see citing works
Self-citationCellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway
Mo, J.-S., Meng, Z., Kim, Y. C., Park, H. W., Hansen, C. G., Kim, S., Lim, D.-S., & Guan, K.-L. (2015) · Nature Cell Biology · doi:10.1038/ncb3111 · Cited by 557 · see citing works
Self-citationComprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer
Wang, Y., Xu, X., Maglic, D., Dill, M. T., Mojumdar, K., Ng, P. K.-S., Jeong, K. J., Tsang, Y. H., Moreno, D., Bhavana, V. H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.10.001 · Cited by 500 · see citing works
Aerobic glycolysis tunes YAP/TAZ transcriptional activity
Enzo, E., Santinon, G., Pocaterra, A., Aragona, M., Bresolin, S., Forcato, M., Grifoni, D., Pession, A., Zanconato, F., Guzzo, G., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490379 · Cited by 414 · see citing works
Geng, J., Sun, X., Wang, P., Zhang, S., Wang, X., Wu, H., Hong, L., Xie, C., Li, X., Zhao, H., et al. (2015) · Nature Immunology · doi:10.1038/ni.3268 · Cited by 264 · see citing works
Regulation of TEAD Transcription Factors in Cancer Biology
Huh, H., Kim, D., Jeong, H.-S., & Park, H. (2019) · Cells · doi:10.3390/cells8060600 · Cited by 259 · see citing works
Hagenbeek, T. J., Zbieg, J. R., Hafner, M., Mroue, R., Lacap, J. A., Sodir, N. M., Noland, C. L., Afghani, S., Kishore, A., Bhat, K. P., et al. (2023) · Nature Cancer · doi:10.1038/s43018-023-00577-0 · Cited by 215 · see citing works
Regulation of YAP by mTOR and autophagy reveals a therapeutic target of tuberous sclerosis complex
Liang, N., Zhang, C., Dill, P., Panasyuk, G., Pion, D., Koka, V., Gallazzini, M., Olson, E. N., Lam, H., Henske, E. P., et al. (2014) · Journal of Experimental Medicine · doi:10.1084/jem.20140341 · Cited by 205 · see citing works
Bone regeneration is mediated by macrophage extracellular vesicles
Kang, M., Huang, C.-C., Lu, Y., Shirazi, S., Gajendrareddy, P., Ravindran, S., & Cooper, L. F. (2020) · Bone · doi:10.1016/j.bone.2020.115627 · Cited by 197 · see citing works
Li, P., Silvis, M. R., Honaker, Y., Lien, W.-H., Arron, S. T., & Vasioukhin, V. (2016) · Genes & Development · doi:10.1101/gad.274951.115 · Cited by 180 · see citing works
Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics
Ma, X., Huang, T., Chen, X., Li, Q., Liao, M., Fu, L., Huang, J., Yuan, K., Wang, Z., & Zeng, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02104-8 · Cited by 133 · see citing works
Alveolar rhabdomyosarcoma–associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression
Crose, L. E. S., Galindo, K. A., Kephart, J. G., Chen, C., Fitamant, J., Bardeesy, N., Bentley, R. C., Galindo, R. L., Ashley Chi, J.-T., & Linardic, C. M. (2014) · Journal of Clinical Investigation · doi:10.1172/jci67087 · Cited by 124 · see citing works
MRTF potentiates TEAD‐YAP transcriptional activity causing metastasis
Kim, T., Hwang, D., Lee, D., Kim, J., Kim, S., & Lim, D. (2017) · The EMBO Journal · doi:10.15252/embj.201695137 · Cited by 114 · see citing works
Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation
Alder, O., Cullum, R., Lee, S., Kan, A. C., Wei, W., Yi, Y., Garside, V. C., Bilenky, M., Griffith, M., Morrissy, A. S., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.046 · Cited by 113 · see citing works
“TEAD2 functions as a nuclear TF in the Hippo signaling pathway, which can regulate cell death, proliferation, and differentiation (reviewed in Yu and Guan, 2013).”
BackgroundOxidative stress–CBP axis modulates MOB1 acetylation and activates the Hippo signaling pathway
Jin, J., Zhang, L., Li, X., Xu, W., Yang, S., Song, J., Zhang, W., Zhan, J., Luo, J., & Zhang, H. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac189 · Cited by 99 · see citing works
The Hippo Pathway Effectors TAZ/YAP Regulate Dicer Expression and MicroRNA Biogenesis through Let-7
Chaulk, S. G., Lattanzi, V. J., Hiemer, S. E., Fahlman, R. P., & Varelas, X. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.c113.529362 · Cited by 101 · see citing works
miRNAs that Induce Human Cardiomyocyte Proliferation Converge on the Hippo Pathway
Diez-Cuñado, M., Wei, K., Bushway, P. J., Maurya, M. R., Perera, R., Subramaniam, S., Ruiz-Lozano, P., & Mercola, M. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.049 · Cited by 102 · see citing works
Jiang, Y., Feng, D., Ma, X., Fan, S., Gao, Y., Fu, K., Wang, Y., Sun, J., Yao, X., Liu, C., et al. (2019) · Hepatology · doi:10.1002/hep.30131 · Cited by 103 · see citing works
The Hippo signal transduction network in skeletal and cardiac muscle
Wackerhage, H., Del Re, D. P., Judson, R. N., Sudol, M., & Sadoshima, J. (2014) · Science Signaling · doi:10.1126/scisignal.2005096 · Cited by 92 · see citing works
Mesothelium and Malignant Mesothelioma
Hiriart, E., Deepe, R., & Wessels, A. (2019) · Journal of Developmental Biology · doi:10.3390/jdb7020007 · Cited by 66 · see citing works
A protein tertiary structure mimetic modulator of the Hippo signalling pathway
Adihou, H., Gopalakrishnan, R., Förster, T., Guéret, S. M., Gasper, R., Geschwindner, S., Carrillo García, C., Karatas, H., Pobbati, A. V., Vazquez‐Chantada, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19224-8 · Cited by 58 · see citing works
Hao, F., Xu, Q., Wang, J., Yu, S., Chang, H.-H., Sinnett-Smith, J., Eibl, G., & Rozengurt, E. (2019) · PLOS ONE · doi:10.1371/journal.pone.0216603 · Cited by 55 · see citing works
Regulation of ciliary membrane protein trafficking and signalling by kinesin motor proteins
Morthorst, S. K., Christensen, S. T., & Pedersen, L. B. (2018) · The FEBS Journal · doi:10.1111/febs.14583 · Cited by 49 · see citing works
Lin, Z., & Pu, W. T. (2014) · Stem Cell Research · doi:10.1016/j.scr.2014.04.010 · Cited by 52 · see citing works
Chen, C., Shi, Z., Zhang, W., Chen, M., He, F., Zhang, Z., Wang, Y., Feng, M., Wang, W., Zhao, Y., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.529297 · Cited by 47 · see citing works
Wittkorn, E., Sarkar, A., Garcia, K., Kango-Singh, M., & Singh, A. (2015) · Development · doi:10.1242/dev.117358 · Cited by 39 · see citing works
Yang, W., Zhang, M., Zhang, T.-X., Liu, J.-H., Hao, M.-W., Yan, X., Gao, H., Lei, Q.-Y., Cui, J., & Zhou, X. (2024) · JCI Insight · doi:10.1172/jci.insight.178535 · Cited by 31 · see citing works
“The Hippo pathway is critical in controlling organ size and carcinogenesis (16, 17).”
Liu, B., Sun, L.-H., Huang, Y.-F., Guo, L.-J., & Luo, L.-S. (2018) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.12.015 · Cited by 29 · see citing works
Yang, S., Xu, W., Liu, C., Jin, J., Li, X., Jiang, Y., Zhang, L., Meng, X., Zhan, J., & Zhang, H. (2022) · Science China Life Sciences · doi:10.1007/s11427-020-1914-3 · Cited by 24 · see citing works
Yang, R., Kong, E., Jin, J., Hergovich, A., & Püschel, A. W. (2014) · Journal of Cell Science · doi:10.1242/jcs.146696 · Cited by 25 · see citing works
Freund, E., Miebach, L., Stope, M., & Bekeschus, S. (2021) · Oncology Reports · doi:10.3892/or.2021.8022 · Cited by 18 · see citing works
- Authors
- Yu, F.-X., & Guan, K.-L.
- Affiliations
- University of California San Diego (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-02-15
- Volume
- 27
- Issue
- 4
- Pages
- 355-371
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3589553
- OpenAlex
- W2171501785
- Cited by
- 1,231
- References
- 10
- Citations by year
- 2026: 43 · 2025: 54 · 2024: 74 · 2023: 73 · 2022: 85 · 2021: 106 · 2020: 126 · 2019: 111 · 2018: 124 · 2017: 95 · 2016: 97 · 2015: 111 · 2014: 102 · 2013: 28
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- California Institute for Regenerative Medicine
- National Eye Institute (R01EY022611)
- National Cancer Institute (R01CA132809)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- Hippo signaling pathway, cell number regulation, cell proliferation, cell death, cell differentiation, cell polarity, mechanotransduction, G protein-coupled receptor signaling, actin cytoskeleton, tumor formation, organ degeneration, Drosophila, mammals
- MeSH terms
- Animals, Cytoskeleton, Extracellular Matrix, Gene Expression Regulation, Phosphotransferases, Signal Transduction, Cell Polarity, Receptors, G-Protein-Coupled, Intracellular Signaling Peptides and Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
