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

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Science  29 May 2015:
Vol. 348, Issue 6238, pp. 1024-1027
DOI: 10.1126/science.aaa4559

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Stretching cell sheets promotes proliferation

Mechanical strain regulates the development, organization, and function of multicellular tissues. But how? Cadherins mechanically couple neighboring epithelial cells through extracellular interactions and sequester the transcription factors β-catenin and Yap1. To find out more, Benham-Pyle et al. stretched epithelial cell sheets. This mechanical strain induced rapid cell cycle reentry, DNA synthesis by sequential nuclear accumulation, and transcriptional activation of Yap1 and β-catenin. Thus, cell-cell junctions are mechanically responsive structural scaffolds providing signaling centers that coordinate transcriptional responses to externally applied force.

Science, this issue p. 1024

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.

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