The claudin-transcription factor signaling pathway

Tissue Barriers. 2021 Jul 3;9(3):1908109. doi: 10.1080/21688370.2021.1908109. Epub 2021 Apr 27.


Claudins (CLDNs) represent major transmembrane proteins of tight junctions and contribute to the barrier function. They also serve as anchors for several signaling proteins, but the underlying molecular basis has yet to be established. The present review covers the recent progress in our understanding of the CLDN signaling pathway in health and disease. We discuss the functional relevance of phosphotyrosine motifs in the C-terminal cytoplasmic domain of CLDNs and define mutual regulation between CLDNs and Src-family kinases (SFKs). In addition, we focus on the crosstalk between CLDN and transcription factor signaling. We also describe how aberrant CLDN-transcription factor signaling promotes or inhibits cancer progression. We propose that a link between various cell adhesion molecules and transcription factors coordinates a range of physiological and pathological events via activation or suppression of target genes.

Keywords: AKT; CLDN; PI3K; Src-family kinase; Tight junction; cell adhesion signal; nuclear receptor; signal transduction; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Claudins* / genetics
  • Humans
  • Neoplasms*
  • Signal Transduction
  • Tight Junctions
  • Transcription Factors


  • Claudins
  • Transcription Factors

Grant support

This work was supported by Japan Agency for Medical Research and Development [JP20lm0203010]; Japan Society for the Promotion of Science [19K16615]; Japan Society for the Promotion of Science [17K08699]; Japan Society for the Promotion of Science [17K17978]; the Uehara Memorial Foundation; the Takeda Science Foundation; and the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care.