TY - JOUR TI - Increasing β-catenin/Wnt3A activity levels drive mechanical strain-induced cell cycle progression through mitosis AU - Benham-Pyle, Blair W AU - Sim, Joo Yong AU - Hart, Kevin C AU - Pruitt, Beth L AU - Nelson, William James A2 - Fässler, Reinhard VL - 5 PY - 2016 DA - 2016/10/26 SP - e19799 C1 - eLife 2016;5:e19799 DO - 10.7554/eLife.19799 UR - https://doi.org/10.7554/eLife.19799 AB - Mechanical force and Wnt signaling activate β-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 β-catenin signaling and cell division. We show that mechanical strain induced Src-dependent phosphorylation of Y654 β-catenin and increased β-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 β-catenin through Casein Kinase I inhibition or Wnt3A addition increased β-catenin-mediated transcription and strain-induced accumulation of cells in S/G2. Significantly, only the combination of mechanical strain and Wnt/β-catenin activation triggered cells in S/G2 to divide. These results indicate that strain-induced Src phosphorylation of β-catenin and Wnt-dependent β-catenin stabilization synergize to increase β-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. KW - β-catenin KW - cell cycle KW - Wnt KW - mechanotransduction KW - Src JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -