Journal
ELIFE
Volume 5, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.19799
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Funding
- National Science Foundation [1136790, DGE-114747]
- National Science Foundation Graduate Student Fellowship
- National Institutes of Health [T32GM007276, 11R35GM118064-01]
- Stanford University Bio-X Graduate Fellowship
- Stanford University Lieberman Graduate Fellowship
- Emerging Frontiers & Multidisciplinary Activities
- Directorate For Engineering [1136790] Funding Source: National Science Foundation
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Mechanical force and Wnt signaling activate beta-catenin-mediated transcription to promote proliferation and tissue expansion. However, it is unknown whether mechanical force and Wnt signaling act independently or synergize to activate beta-catenin signaling and cell division. We show that mechanical strain induced Src-dependent phosphorylation of Y654 beta-catenin and increased beta-catenin-mediated transcription in mammalian MDCK epithelial cells. Under these conditions, cells accumulated in S/G2 (independent of DNA damage) but did not divide. Activating beta-catenin through Casein Kinase I inhibition or Wnt3A addition increased beta-catenin-mediated transcription and strain-induced accumulation of cells in S/G2. Significantly, only the combination of mechanical strain and Wnt/beta-catenin activation triggered cells in S/G2 to divide. These results indicate that strain-induced Src phosphorylation of beta-catenin and Wnt-dependent beta-catenin stabilization synergize to increase beta-catenin-mediated transcription to levels required for mitosis. Thus, local Wnt signaling may fine-tune the effects of global mechanical strain to restrict cell divisions during tissue development and homeostasis.
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