Publication Date:
2015-05-30
Description:
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 beta-catenin. Inhibition of Yap1- and beta-catenin-mediated transcription blocked cell cycle reentry and progression through G1 into S phase, respectively. Maintenance of quiescence, Yap1 nuclear exclusion, and beta-catenin transcriptional responses to mechanical strain required E-cadherin extracellular engagement. Thus, activation of Yap1 and beta-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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572847/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572847/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Benham-Pyle, Blair W -- Pruitt, Beth L -- Nelson, W James -- EB006745/EB/NIBIB NIH HHS/ -- GM 35527/GM/NIGMS NIH HHS/ -- R01 GM035527/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 May 29;348(6238):1024-7. doi: 10.1126/science.aaa4559.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Cancer Biology, Stanford University, Stanford, CA 94305, USA. ; 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. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26023140" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing/*biosynthesis/metabolism
;
Animals
;
Cadherins/*metabolism
;
Cell Adhesion/genetics
;
Cell Cycle/*genetics
;
Cell Nucleus/metabolism
;
Cell Proliferation
;
Dogs
;
Epithelial Cells/cytology/metabolism/physiology
;
Madin Darby Canine Kidney Cells
;
Phosphoproteins/*biosynthesis/metabolism
;
*Stress, Mechanical
;
*Transcription, Genetic
;
beta Catenin/*biosynthesis/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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