Increasing β-catenin/Wnt3A activity levels drive mechanical strain-induced cell cycle progression through mitosis.

Abstract:

: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.

journal_name

Elife

journal_title

eLife

authors

Benham-Pyle BW,Sim JY,Hart KC,Pruitt BL,Nelson WJ

doi

10.7554/eLife.19799

subject

Has Abstract

pub_date

2016-10-26 00:00:00

issn

2050-084X

journal_volume

5

pub_type

杂志文章

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