Mechanical strain induces E-cadherin–dependent Yap1 and β-catenin activation to drive cell cycle entry
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TLDR
It is shown that mechanical strain applied to quiescent epithelial cells induced rapid cell cycle reentry, mediated by independent nuclear accumulation and transcriptional activity of first Yap1 and then β-catenin, and cadherins provide signaling centers required for cellular responses to externally applied force.Abstract:
Mechanical strain regulates the development, organization, and function of multicellular tissues, but mechanisms linking mechanical strain and cell-cell junction proteins to cellular responses are poorly understood. Here, we showed that mechanical strain applied to quiescent epithelial cells induced rapid cell cycle reentry, mediated by independent nuclear accumulation and transcriptional activity of first Yap1 and then β-catenin. Inhibition of Yap1- and β-catenin-mediated transcription blocked cell cycle reentry and progression through G1 into S phase, respectively. Maintenance of quiescence, Yap1 nuclear exclusion, and β-catenin transcriptional responses to mechanical strain required E-cadherin extracellular engagement. Thus, activation of Yap1 and β-catenin may represent a master regulator of mechanical strain-induced cell proliferation, and cadherins provide signaling centers required for cellular responses to externally applied force.read more
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Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer.
TL;DR: The Hippo pathway regulates cell proliferation, apoptosis, and stemness in response to a wide range of extracellular and intracellular signals, including cell-cell contact, cell polarity, mechanical cues, ligands of G-protein-coupled receptors, and cellular energy status.
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YAP/TAZ at the Roots of Cancer
TL;DR: In this paper, a number of cancer-associated extrinsic and intrinsic cues conspire to overrule the YAP-inhibiting microenvironment of normal tissues, including changes in mechanotransduction, inflammation, oncogenic signaling, and regulation of the Hippo pathway.
Journal ArticleDOI
Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores
Alberto Elosegui-Artola,Ion Andreu,Ion Andreu,Amy E. M. Beedle,Amy E. M. Beedle,Ainhoa Lezamiz,Ainhoa Lezamiz,Marina Uroz,Anita Joanna Kosmalska,Roger Oria,Jenny Z. Kechagia,Palma Rico-Lastres,Palma Rico-Lastres,Anabel-Lise Le Roux,Catherine M. Shanahan,Xavier Trepat,Daniel Navajas,Sergi Garcia-Manyes,Sergi Garcia-Manyes,Pere Roca-Cusachs +19 more
TL;DR: This work shows that force applied to the nucleus directly drives YAP nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport, demonstrated for YAP but with potential general applicability in transcriptional regulation.
Journal ArticleDOI
Mechanobiology of YAP and TAZ in physiology and disease
TL;DR: 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.
Journal ArticleDOI
YAP/TAZ upstream signals and downstream responses
TL;DR: How the transcriptional regulators YAP and TAZ integrate mechanical cues with the response to soluble signals and metabolic pathways to control multiple aspects of cell behaviour, including proliferation, cell plasticity and stemness essential for tissue regeneration is reviewed.
References
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