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Journal Article
Increasing β-catenin/Wnt3A activity levels drive mechanical strain-induced cell cycle progression through mitosis
- Authors
- Blair W Benham-Pyle, Joo Yong Sim, Kevin C Hart, Beth L Pruitt, William James Nelson
- Issue Date
- 2016-10
- Citation
- eLife, v.5, pp.1-28
- ISSN
- 2050-084X
- Language
- English
- Type
- Journal Article
- Abstract
- Mechanical force and Wnt signaling activate 棺-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 棺 -catenin signaling and cell division. We show that mechanical strain induced Src-dependent phosphorylation of Y654 棺 -catenin and increased 棺 -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 棺 -catenin through Casein Kinase I inhibition or Wnt3A addition increased 棺 -catenin-mediated transcription and strain-induced accumulation of cells in S/G2. Significantly, only the combination of mechanical strain and Wnt/ 棺 -catenin activation triggered cells in S/G2 to divide. These results indicate that strain-induced Src phosphorylation of 棺 -catenin and Wnt-dependent 棺 -catenin stabilization synergize to increase b-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.
- KSP Keywords
- Casein kinase, Cell Division, Cell cycle progression, DNA Damage, Epithelial cells, Strain-induced, Tissue development, Tissue expansion, Wnt signaling, mechanical force, mechanical strain
This work is distributed under the term of Creative Commons License (CCL)
(CC BY)
(CC BY)
