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Cited by 1,461Hippo pathway signaling and YAP/TAZCellular Mechanics and InteractionsTGF-β signaling in diseases

Mechanobiology of YAP and TAZ in physiology and disease

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Panciera, Tito, Azzolin, Luca, Cordenonsi, Michelangelo, Piccolo, Stefano·2017·Nature Reviews Molecular Cell Biology
DOI 10.1038/nrm.2017.87PMC PMC6192510
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Abstract

A growing body of evidence suggests that mechanical signals emanating from the cell's microenvironment are fundamental regulators of cell behaviour. Moreover, at the macroscopic scale, the influence of forces, such as the forces generated by blood flow, muscle contraction, gravity and overall tissue rigidity (for example, inside of a tumour lump), is central to our understanding of physiology and disease pathogenesis. Still, how mechanical cues are sensed and transduced at the molecular level to regulate gene expression has long remained enigmatic. The identification of the transcription factors YAP and TAZ as mechanotransducers started to fill this gap. YAP and TAZ read a broad range of mechanical cues, from shear stress to cell shape and extracellular matrix rigidity, and translate them into cell-specific transcriptional programmes. YAP and TAZ mechanotransduction is critical for driving stem cell behaviour and regeneration, and it sheds new light on the mechanisms by which aberrant cell mechanics is instrumental for the onset of multiple diseases, such as atherosclerosis, fibrosis, pulmonary hypertension, inflammation, muscular dystrophy and cancer.

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  • CAFs secrete MMPs including MMP-2, MMP-3, and MMP-9, or activate Yes-associated protein to promote ECM degradation and remodeling, EMT, and CSC stemness.

    “CAFs reportedly secrete matrix metalloproteinases (MMPs), including MMP-2, MMP-3, and MMP-9, or activate Yes-associated protein to promote ECM degradation and remodeling, EMT, and CSC stemness.283–287”

    From Drug repurposing for cancer therapy (2024) · cites this paper as [287]

    In “Instructive roles of YAP and TAZ in cancer development” (page unavailable), the paper links CAFs to metalloprotease-mediated ECM remodelling and says YAP activation in CAFs promotes ECM restructuring. It also links active YAP/TAZ to cancer stem cells. It does not identify MMP-2, MMP-3, or MMP-9 as CAF secretions, or establish the claimed CAF–YAP pathway to EMT and CSC stemness. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Panciera, T., Azzolin, L., Cordenonsi, M., & Piccolo, S.
Affiliations
University of Padua (IT)
Corresponding author
Piccolo, Stefano
ORCID
Venue
Nature Reviews Molecular Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2017-09-27
Volume
18
Issue
12
Pages
758-770
ISSN
  • 1471-0072 (ISSN-L)
  • 1471-0080
DOI
10.1038/nrm.2017.87
PMC
PMC6192510
OpenAlex
W2758838459
Cited by
1,461
References
15
Citations by year
2026: 245 · 2025: 187 · 2024: 178 · 2023: 172 · 2022: 183 · 2021: 156 · 2020: 158 · 2019: 100 · 2018: 76 · 2017: 4
FWCI
10.78
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Molecular Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion, other-oa)
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 › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
YAP, TAZ, mechanotransduction, mechanobiology, transcription factors, cell mechanics, extracellular matrix stiffness, shear stress, cell shape, tissue regeneration, atherosclerosis, fibrosis, pulmonary hypertension, inflammation, muscular dystrophy, cancer, tumor stiffness
MeSH terms
YAP-Signaling Proteins, Acyltransferases, Animals, Extracellular Matrix, Fibrosis, Humans, Hypertension, Pulmonary, Muscular Dystrophies, Neoplasms, Phosphoproteins, Transcription Factors, Transcription, Genetic, Shear Strength, Mechanotransduction, Cellular, Cell Shape, Adaptor Proteins, Signal Transducing, Atherosclerosis

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