Journal ArticleDOI
Role of YAP/TAZ in mechanotransduction
Sirio Dupont,Leonardo Morsut,Mariaceleste Aragona,Elena Enzo,Stefano Giulitti,Michelangelo Cordenonsi,Francesca Zanconato,Jimmy Le Digabel,Mattia Forcato,Silvio Bicciato,Nicola Elvassore,Stefano Piccolo +11 more
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TLDR
YAP/TAZ are identified as sensors and mediators of mechanical cues instructed by the cellular microenvironment and are functionally required for differentiation of mesenchymal stem cells induced by ECM stiffness and for survival of endothelial cells regulated by cell geometry.Abstract:
Cells perceive their microenvironment not only through soluble signals but also through physical and mechanical cues, such as extracellular matrix (ECM) stiffness or confined adhesiveness. By mechanotransduction systems, cells translate these stimuli into biochemical signals controlling multiple aspects of cell behaviour, including growth, differentiation and cancer malignant progression, but how rigidity mechanosensing is ultimately linked to activity of nuclear transcription factors remains poorly understood. Here we report the identification of the Yorkie-homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1) as nuclear relays of mechanical signals exerted by ECM rigidity and cell shape. This regulation requires Rho GTPase activity and tension of the actomyosin cytoskeleton, but is independent of the Hippo/LATS cascade. Crucially, YAP/TAZ are functionally required for differentiation of mesenchymal stem cells induced by ECM stiffness and for survival of endothelial cells regulated by cell geometry; conversely, expression of activated YAP overrules physical constraints in dictating cell behaviour. These findings identify YAP/TAZ as sensors and mediators of mechanical cues instructed by the cellular microenvironment.read more
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Journal ArticleDOI
Actin Cytoskeleton Regulates Hippo Signaling
TL;DR: It is shown that actin cytoskeleton is one of the upstream regulators of Hippo signaling capable of activating YAP and increasing its downstream CCN growth factors.
Journal ArticleDOI
miR-135b, upregulated in breast cancer, promotes cell growth and disrupts the cell cycle by regulating LATS2
Kaiyao Hua,Jiali Jin,Junyong Zhao,Jialu Song,Hongming Song,Dengfeng Li,Niraj Maskey,Bingkun Zhao,Chenyang Wu,Hui Xu,Lin Fang +10 more
TL;DR: The experiments indicate that expression of miR-135b was commonly upregulated in breast cancer specimens and breast cancer cells when compared with that in adjacent normal tissues and non-malignant breast epithelial cells, and demonstrate that the downstream gene of LATS2 in the Hippo pathway, such as cyclin-dependent kinase 2 (CDK2) and Phospho-Yes-associated protein (p-YAP), can also be regulated by miR
Journal ArticleDOI
Roles of the Hippo pathway in lung development and tumorigenesis.
TL;DR: The most recent advances are summarized, future directions on this new cancer research field are predicted and the Hippo pathway may play important roles in not only lung development but also lung tumorigenesis are predicted.
Journal ArticleDOI
Cell competition in development: information from flies and vertebrates.
TL;DR: An account of recent advances which help summarize the mechanisms of operation and growing role of cell competition in regulation of oncogenesis in vertebrates are provided.
Journal ArticleDOI
The Roles of YAP/TAZ and the Hippo Pathway in Healthy and Diseased Skin.
Emanuel Rognoni,Gernot Walko +1 more
TL;DR: The current knowledge of how the Hippo pathway and its downstream effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) contribute to the maintenance, activation and coordination of the epidermal and dermal cell populations during development, homeostasis, wound healing and cancer is discussed.
References
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Journal ArticleDOI
Matrix elasticity directs stem cell lineage specification.
TL;DR: Naive mesenchymal stem cells are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types.
Journal ArticleDOI
Geometric control of cell life and death.
TL;DR: Human and bovine capillary endothelial cells were switched from growth to apoptosis by using micropatterned substrates that contained extracellular matrix-coated adhesive islands of decreasing size to progressively restrict cell extension.
Journal ArticleDOI
Cell shape, cytoskeletal tension, and rhoa regulate stem cell lineage commitment
TL;DR: It is demonstrated that cell shape regulates commitment of human mesenchymal stem cells to adipocyte or osteoblast fate and mechanical cues experienced in developmental and adult contexts, embodied by cell shape, cytoskeletal tension, and RhoA signaling, are integral to the commitment of stem cell fate.
Journal ArticleDOI
Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control
Bin Zhao,Xiaomu Wei,Weiquan Li,Ryan S. Udan,Ryan S. Udan,Qian Yang,Joungmok Kim,Joungmok Kim,Joe Xie,Tsuneo Ikenoue,Jindan Yu,Li Li,Li Li,Pan Zheng,Keqiang Ye,Arul M. Chinnaiyan,Georg Halder,Georg Halder,Zhi Chun Lai,Kun-Liang Guan,Kun-Liang Guan +20 more
TL;DR: It is demonstrated that in mammalian cells, the transcription coactivator YAP (Yes-associated protein), is inhibited by cell density via the Hippo pathway, and YAP overexpression regulates gene expression in a manner opposite to cell density, and is able to overcome cell contact inhibition.
Journal ArticleDOI
Local force and geometry sensing regulate cell functions.
Viola Vogel,Michael P. Sheetz +1 more
TL;DR: Tissue scaffolds that have been engineered at the micro- and nanoscale level now enable better dissection of the mechanosensing, transduction and response mechanisms of eukaryotic cells.