2. Academic Validation
  3. FAK mediates mechanical signaling to maintain epithelial homeostasis through YAP/TAZ-TEADs

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

  • Histochem Cell Biol. 2025 Feb 7;163(1):31. doi: 10.1007/s00418-025-02360-x.
Yang Peng 1,  Qiuyun Yuan 1,  Shuting Zhou 1,  Jianguo Gan 1,  Zhengzhong Shen 1,  Xiaoqiang Xia 1,  Yuchen Jiang 1,  Qianming Chen 2,  Yao Yuan 1,  Gu He 3,  Qiang Wei 4,  Xiaodong Feng 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Frontier Innovation Center for Dental Medicine Plus and Research Unit of Oral Carcinogenesis and Management and Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
  • 2 Key Laboratory of Oral Biomedical Research of Zhejiang Province, Affiliated Stomatology Hospital, Zhejiang University School of Stomatology, Hangzhou, 310000, China.
  • 3 Department of Dermatology and Venerology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • 4 College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials and Engineering, Sichuan University, Chengdu, 610065, China. wei@scu.edu.cn.
  • 5 State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Frontier Innovation Center for Dental Medicine Plus and Research Unit of Oral Carcinogenesis and Management and Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China. xiaodongfeng@scu.edu.cn.
PMID: 39918604 DOI: 10.1007/s00418-025-02360-x
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.

Keywords

Epithelial homeostasis; FAK; Keratinocyte; Mechanical signaling; YAP/TAZ.

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