DNA demethylation of claudin-4 suppresses migration and invasion in laryngeal squamous carcinoma cells.

Claudin-4 (CLDN4) is a member of the claudin transmembrane protein family, which consists of integral membrane proteins that are components of the epithelial cell tight junctions; these tight junctions regulate movement of solutes and ions through the paracellular space. CLDN4 is also a differentiation marker and is believed to indicate an epithelial phenotype. However, the role of CLDN4 in laryngeal squamous carcinoma is still unclear. Here, we showed that CLDN4 expression was down-regulated in laryngeal squamous carcinoma tissues and negatively correlated with methyl-CpG-binding protein 2. In addition, CLDN4 was hypermethylated in HEp-2 cells. DNA demethylation of CLDN4 by 5-aza-2'-deoxycytidine suppressed migration and invasion of HEp-2 cells, whereas CLDN4 silencing restored the migration and invasion of HEp-2 cells. Therefore, CLDN4 plays a key role in laryngeal squamous carcinoma progression.