Cadherins and growth factor receptors: Signaling mechano-switches at intercellular junctions

This review focuses on recent findings that cadherins, like integrins, mechanically initiate signaling cascades that can share elements with integrins but have distinct biological functions. Specifically, we focus on evidence that cadherins and receptor tyrosine kinases (RTKs) form mechano-switches at intercellular junctions that regulate the integrity of barrier tissues, global cell mechanics, and cell proliferation. Epithelial E-cadherin force transduction signaling is further discussed in the context of other cadherin-mediated intercellular signaling that regulates Hippo kinases and YAP localization. This article highlights similarities and differences in force transduction by three, different classical cadherins and argues that cadherins and specific RTK partners constitute general intercellular mechano-switches, with tissue-specific functions. Several examples presented demonstrate the physiological significance of this force activated cadherin/RTK signal transduction mechanism and suggest how mechanically regulated, cadherin-dependent signaling could be harnessed to tune tissue-specific functions.