The Hippo Pathway: Biology and Pathophysiology
Abstract
The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size control, and regeneration. The core of the Hippo pathway in mammals consists of a kinase cascade, MST1/2 and LATS1/2, as well as downstream effectors, transcriptional coactivators YAP and TAZ. These core components of the Hippo pathway control transcriptional programs involved in cell proliferation, survival, mobility, stemness, and differentiation. The Hippo pathway is tightly regulated by both intrinsic and extrinsic signals, such as mechanical force, cell–cell contact, polarity, energy status, stress, and many diffusible hormonal factors, the majority of which act through G protein–coupled receptors. Here, we review the current understanding of molecular mechanisms by which signals regulate the Hippo pathway with an emphasis on mechanotransduction and the effects of this pathway on basic biology and human diseases.
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The Hippo pathway controls the YAP-TAZ-TEAD transcriptional complex that promotes expression of genes important for cancer cell proliferation, survival, and progression.
“The Hippo pathway controls the YAP-TAZ-TEAD transcriptional complex that promotes the expression of genes important for cancer cell proliferation, survival, and progression (26–28).”
From Targeting eIF4A-dependent translation in genetically complex sarcoma (2026) · cites this paper as [28]
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BackgroundAMPK modulates Hippo pathway activity to regulate energy homeostasis
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Targeting eIF4A-dependent translation in genetically complex sarcoma
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- Authors
- Ma, S., Meng, Z., Chen, R., & Guan, K.-L.
- Affiliations
- University of California San Diego (US)
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2019-06-20
- Volume
- 88
- Issue
- 1
- Pages
- 577-604
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- OpenAlex
- W2905097208
- Cited by
- 1,387
- References
- 17
- Citations by year
- 2026: 145 · 2025: 257 · 2024: 292 · 2023: 257 · 2022: 196 · 2021: 133 · 2020: 78 · 2019: 26 · 2018: 1 · 2017: 1
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- 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 › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- Hippo signaling pathway, MST1/2, LATS1/2, YAP, TAZ, organ size control, tissue growth regulation, mechanotransduction, cell-cell contact, cell polarity, energy status, G protein-coupled receptors, cell proliferation, stemness, regeneration, disease pathophysiology
- MeSH terms
- Hippo Signaling Pathway, Serine-Threonine Kinase 3, Hippo Kinases, Animals, Humans, Signal Transduction, Protein Serine-Threonine Kinases, Tumor Suppressor Proteins, Mechanotransduction, Cellular
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