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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Regulation of Hippo pathway by mitogenic growth factors via phosphoinositide 3-kinase and phosphoinositide-dependent kinase-1
TL;DR: Findings show that an important activity of mitogenic signaling pathways is to inactivate the growth-inhibitory Hippo pathway and provide a mechanism for antagonism between contact inhibition and growth factor action.
Journal ArticleDOI
Aerobic glycolysis tunes YAP/TAZ transcriptional activity
Elena Enzo,Giulia Santinon,Arianna Pocaterra,Mariaceleste Aragona,Silvia Bresolin,Mattia Forcato,Daniela Grifoni,Annalisa Pession,Francesca Zanconato,Giulia Guzzo,Silvio Bicciato,Sirio Dupont +11 more
TL;DR: Findings suggest that aerobic glycolysis endows cancer cells with particular metabolic properties and at the same time sustains transcription factors with potent pro‐tumorigenic activities such as YAP/TAZ.
Journal ArticleDOI
Asymmetric division of contractile domains couples cell positioning and fate specification
Jean-Léon Maître,Hervé Turlier,Rukshala Illukkumbura,Björn Eismann,Ritsuya Niwayama,François Nédélec,Takashi Hiiragi +6 more
TL;DR: It is proposed that contractility couples the positioning and fate specification of blastomeres, which ensures the robust self-organization ofblastomeres into the blastocyst, which confers remarkable regulative capacities to mammalian embryos.
Journal ArticleDOI
Tissue mechanics and fibrosis
TL;DR: Better understanding of the variety and magnitude of forces, the characteristics of those forces in biological tissues, and their impact on fibrosis in multiple tissues is needed and may lead to identification of important new therapeutic targets.
Journal ArticleDOI
Cytokinesis failure triggers hippo tumor suppressor pathway activation.
Neil J. Ganem,Hauke Cornils,Shang-Yi Chiu,Kevin P. O’Rourke,Jonathan Arnaud,Dean Yimlamai,Manuel Théry,Fernando D. Camargo,David Pellman +8 more
TL;DR: It is demonstrated that cytokinesis failure activates the Hippo tumor suppressor pathway in cultured cells, as well as in naturally occurring tetraploid cells in vivo, defining an important tumor suppression mechanism and uncover adaptive mechanisms potentially available to nascent tumor cells that bypass this inhibitory regulation.
References
More filters
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.