Mechanical strain induces E-cadherin-dependent Yap1 and β-catenin activation to drive cell cycle entry

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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2015-05, Vol.348 (6238), p.1024-1027
Main Authors: Benham-Pyle, Blair W., Pruitt, Beth L., Nelson, W. James
Format: Article
Language:English
Subjects:
Activation
Cellular
Joining
Organizations
Progressions
Reentry
Regulators
Strain
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aaa4559