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Control of cellular responses to mechanical cues through YAP/TAZ regulation
Open accessAbstract
To perceive their three-dimensional environment, cells and tissues must be able to sense and interpret various physical forces like shear, tensile, and compression stress. These forces can be generated both internally and externally in response to physical properties, like substrate stiffness, cell contractility, and forces generated by adjacent cells. Mechanical cues have important roles in cell fate decisions regarding proliferation, survival, and differentiation as well as the processes of tissue regeneration and wound repair. Aberrant remodeling of the extracellular space and/or defects in properly responding to mechanical cues likely contributes to various disease states, such as fibrosis, muscle diseases, and cancer. Mechanotransduction involves the sensing and translation of mechanical forces into biochemical signals, like activation of specific genes and signaling cascades that enable cells to adapt to their physical environment. The signaling pathways involved in mechanical signaling are highly complex, but numerous studies have highlighted a central role for the Hippo pathway and other signaling networks in regulating the YAP and TAZ (YAP/TAZ) proteins to mediate the effects of mechanical stimuli on cellular behavior. How mechanical cues control YAP/TAZ has been poorly understood. However, rapid progress in the last few years is beginning to reveal a surprisingly diverse set of pathways for controlling YAP/TAZ. In this review, we will focus on how mechanical perturbations are sensed through changes in the actin cytoskeleton and mechanosensors at focal adhesions, adherens junctions, and the nuclear envelope to regulate YAP/TAZ.
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“However, beyond acting as a physical barrier, ECM stiffness also triggers mechanotransduction pathways that profoundly influence tumor cell behavior [91,92]. Mechanical cues generated by a stiffened matrix are sensed through integrin-based focal adhesions and transmitted via cytoskeletal tension to activate intracellular signaling cascades, including Yes-associated protein/Transcriptional coactiv”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [95]
In the citing paper
“Similarly, the Hippo pathway has gained attention as an important pathway in mechanotransduction and skeletal physiology. Downstream YAP/TAZ regulation is in fact tightly involved in mechanosensing and mechanotransduction both in bone and muscle as well as in many other cells, especially endothelial cells (see Section 3.3).”
From Interactions between Muscle and Bone—Where Physics Meets Biology (2020) · cites this paper as [55]
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Metadata
- Authors
- Dasgupta, I., & McCollum, D.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- McCollum, Dannel
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 294
- Issue
- 46
- Pages
- 17693-17706
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC6873206
- OpenAlex
- W2980104037
- Cited by
- 360
- References
- 138
- Citations by year
- 2026: 47 · 2025: 57 · 2024: 49 · 2023: 64 · 2022: 45 · 2021: 64 · 2020: 33 · 2019: 1
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- National Institutes of Health (RO1 GM058406)
- 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 › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- YAP/TAZ, mechanotransduction, Hippo signaling pathway, mechanical cues, substrate stiffness, actin cytoskeleton, focal adhesions, adherens junctions, nuclear envelope, mechanosensors, cell fate determination, tissue regeneration, fibrosis, cancer
- MeSH terms
- YAP-Signaling Proteins, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Animals, Humans, Actin Cytoskeleton, Transcription Factors, Signal Transduction, Trans-Activators, Focal Adhesions, Adherens Junctions, Mechanotransduction, Cellular, Adaptor Proteins, Signal Transducing
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