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The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal
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Precise control of organ size is crucial during animal development and regeneration. In Drosophila and mammals, studies over the past decade have uncovered a critical role for the Hippo tumour-suppressor pathway in the regulation of organ size. Dysregulation of this pathway leads to massive overgrowth of tissue. The Hippo signalling pathway is highly conserved and limits organ size by phosphorylating and inhibiting the transcription co-activators YAP and TAZ in mammals and Yki in Drosophila, key regulators of proliferation and apoptosis. The Hippo pathway also has a critical role in the self-renewal and expansion of stem cells and tissue-specific progenitor cells, and has important functions in tissue regeneration. Emerging evidence shows that the Hippo pathway is regulated by cell polarity, cell adhesion and cell junction proteins. In this review we summarize current understanding of the composition and regulation of the Hippo pathway, and discuss how cell polarity and cell adhesion proteins inform the role of this pathway in organ size control and regeneration.
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“some important signaling pathways involved in regulation of stem cell self‐renewal, including MAPK,[ 32 , 33 ] JAK‐STAT,[ 34 ] Hippo,[ 35 ] and FoxO[ 36 ] pathways, were upregulated in ISO‐treated HEKs (Figure S5b, Supporting Information).”
From Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin (2021) · cites this paper as [35]
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Metadata
- Authors
- Zhao, B., Tumaneng, K., & Guan, K.-L.
- Affiliations
- Zhejiang University (CN)
- University of California San Diego (US)
- Corresponding author
- Guan, Kun-Liang
- Venue
- Nature Cell Biology
- Published
- 2011-08
- Volume
- 13
- Issue
- 8
- Pages
- 877-883
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC3987945
- OpenAlex
- W2033360354
- Cited by
- 1,205
- References
- 130
- Citations by year
- 2026: 29 · 2025: 53 · 2024: 69 · 2023: 66 · 2022: 110 · 2021: 105 · 2020: 90 · 2019: 97 · 2018: 102 · 2017: 70 · 2016: 80 · 2015: 94 · 2014: 88 · 2013: 88 · 2012: 61
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA132809)
- National Institute of General Medical Sciences (R01GM051586, T32GM007752)
- 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 › Developmental Biology and Gene Regulation
- Keywords
- Hippo signaling pathway, organ size control, tissue regeneration, stem cell self-renewal, YAP, TAZ, Yki, cell polarity, cell adhesion, cell junction proteins, tumor suppression, tissue overgrowth, Drosophila, mammals
- MeSH terms
- Hippo Kinases, Animals, Cell Adhesion, Drosophila, Humans, Intercellular Junctions, Models, Biological, Organ Size, Regeneration, Stem Cells, Signal Transduction, Cell Polarity, Protein Serine-Threonine Kinases, Drosophila Proteins, Intracellular Signaling Peptides and Proteins, Mice
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