Portal de Periódicos da CAPES

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

2015; American Association for the Advancement of Science; Volume: 348; Issue: 6238 Linguagem: Inglês

10.1126/science.aaa4559

1095-9203

Blair W. Benham-Pyle, Beth L. Pruitt, W. James Nelson,

RNA Research and Splicing

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.