Claudin Proteins in Epithelial Barrier Function and Cancer

Claudins are a family of tetraspan membrane proteins that constitute the structural and functional core of tight junctions, which maintain epithelial barrier integrity by controlling selective paracellular passage of ions and solutes. Distinct claudin isoforms exhibit tissue-specific expression patterns that confer unique charge and size selectivity to paracellular channels, underpinning organ-specific barrier properties. Dysregulated claudin expression has been linked to carcinogenesis through disruption of epithelial polarity, modulation of cell–matrix interactions and engagement of intracellular signalling pathways. Emerging evidence indicates that certain claudins can function as context-dependent tumour suppressors or promoters, influencing cancer cell behaviour via mechanisms such as autophagy, lipid metabolism and growth-factor signalling. These dual roles highlight claudins as mechanistic mediators of barrier dysfunction and as promising biomarkers or therapeutic targets in epithelial malignancies.

Research from Nature Portfolio

Recent studies have revealed that the less-characterised claudin-23 isoform enriches luminal intestinal epithelia and strengthens barrier function by assembling into heteromeric complexes with claudin-3 and claudin-4. Advanced imaging and computational modelling show that these complexes adopt distinct pore architectures, with interaction-dependent charge distributions that regulate paracellular ion and macromolecule permeability. These findings refine the model of tight junction organisation by demonstrating that variable stoichiometries of claudin subunits can generate multiple, functionally discrete paracellular channels.

Claudin Proteins in Epithelial Barrier Function and Cancer publication trend

The graph below shows the total number of articles in claudin proteins in epithelial barrier function and cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Claudins: integral membrane proteins forming the backbone of tight junction strands in epithelial cells.

Tight junctions: specialised cell–cell adhesion structures that seal the intercellular space and regulate paracellular permeability.

Paracellular permeability: selective movement of ions and solutes between adjacent cells, controlled by tight junction composition.

Autophagy: intracellular degradation and recycling process mediated by lysosomes, often linked to cell survival and stress responses.

Tissue microarray: high-throughput technique for simultaneous immunohistochemical analysis of protein expression in multiple tissue samples.

Prognostic marker: a biological factor whose presence or level correlates with disease outcome or progression.

References

1. Claudin-23 reshapes epithelial tight junction architecture to regulate barrier function. Nature Communications (2023).
2. CLDN6 inhibits breast cancer metastasis through WIP-dependent actin cytoskeleton-mediated autophagy. Journal of Experimental & Clinical Cancer Research (2023).
3. Prevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samples. Biomarker Research (2024).
4. Emerging Roles of Claudins in Human Cancer. International Journal of Molecular Sciences (2013).