title: Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and β-catenin activation to drive cell cycle entry.
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.
authors.affiliation: Program in Cancer Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Blair W
authors.initials: BW
authors.lastname: Benham-Pyle
authors.affiliation: Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA. Department of Mechanical Engineering, Stanford University, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Beth L
authors.initials: BL
authors.lastname: Pruitt
authors.affiliation: Program in Cancer Biology, Stanford University, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA. Department of Biology, Stanford University, Stanford, CA 94305, USA. wjnelson@stanford.edu.
authors.forename: W James
authors.initials: WJ
authors.lastname: Nelson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D061985:Madin Darby Canine Kidney Cells; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000378:metabolism; D013314:Stress, Mechanical; D014158:Transcription, Genetic; D051176:beta Catenin / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D010750:Phosphoproteins; D051176:beta Catenin