A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors - PubMed (original) (raw)

. 2013 Aug 29;154(5):1047-1059.

doi: 10.1016/j.cell.2013.07.042. Epub 2013 Aug 15.

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A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors

Mariaceleste Aragona et al. Cell. 2013.

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Abstract

Key cellular decisions, such as proliferation or growth arrest, typically occur at spatially defined locations within tissues. Loss of this spatial control is a hallmark of many diseases, including cancer. Yet, how these patterns are established is incompletely understood. Here, we report that physical and architectural features of a multicellular sheet inform cells about their proliferative capacity through mechanical regulation of YAP and TAZ, known mediators of Hippo signaling and organ growth. YAP/TAZ activity is confined to cells exposed to mechanical stresses, such as stretching, location at edges/curvatures contouring an epithelial sheet, or stiffness of the surrounding extracellular matrix. We identify the F-actin-capping/severing proteins Cofilin, CapZ, and Gelsolin as essential gatekeepers that limit YAP/TAZ activity in cells experiencing low mechanical stresses, including contact inhibition of proliferation. We propose that mechanical forces are overarching regulators of YAP/TAZ in multicellular contexts, setting responsiveness to Hippo, WNT, and GPCR signaling.

Copyright © 2013 Elsevier Inc. All rights reserved.

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