FAK mediates mechanical signaling to maintain epithelial homeostasis through YAP/TAZ-TEADs

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Abstract
Epithelial homeostasis ensures that the epithelium can perform its normal physiological functions. Mechanical signaling response through integrin-mediated adhesions of the basement membrane (BM) is crucial for maintaining epithelial homeostasis. The essential mechanosensors YAP and the paralog TAZ (YAP/TAZ) have been shown to play a critical role in epithelial homeostasis, but the key regulator that mediates mechanical signaling to YAP/TAZ in maintaining epithelial homeostasis has not been fully understood. In this study, we noticed that mechanical signals correlated with YAP/TAZ activation and basal state maintenance in epithelial stem/progenitor cells through immunohistochemistry. Subsequently, we found that inhibition of focal adhesion kinase (FAK) suppressed YAP/TAZ activation in the human keratinocyte line HaCaT cells. Furthermore, inhibition of the interaction between YAP/TAZ and the transcriptional enhanced associate domains (TEADs) resulted in the differentiation of HaCaT cells. Finally, we used primary mouse epithelial cells to reconstruct the epithelium in vitro and found that FAK inhibition led to both a reduction in YAP/TAZ activity and an increase of differentiation in the basal layer cells. In conclusion, our findings reveal that FAK mediates mechanical signaling to maintain epithelial homeostasis via YAP/TAZ-TEADs.
Funding Information
  • Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS, 2019-I2M-5-004)
  • National Natural Science Foundations of China (32200577)
  • National Natural Science Foundations of China (82373187)
  • Scientific Research Foundation, West China Hospital of Stomatology Sichuan University (RD-03-202110)
  • Scientific Research Foundation, West China Hospital of Stomatology Sichuan University (QDJF2019-3)
  • Fundamental Research Funds for the Central Universities (YJ201987)

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