Fig. 6

A Model for transcriptional silencing of CLDN11 through hypermethylation promotes migration by derepression of tubulin polymerization. In a normal nasopharynx, CLDN11 is transcriptionally activated by transcription activators, GATA1 and GATA2. The integral membrane tight junction protein CLDN11, expressed on the apical surface of the epithelial cells, maintains tight junction integrity and epithelial cell polarity and morphology. In addition, CLDN11 serves as the scaffold to recruit tubulins through its intracellular loop and C-terminal domains. The interaction between CLDN11 and the tubulins TUBA1B and TUBB3 may sequester the availability of α- and β-tubulin subunits in the cytoplasm. Thus, the presence of CLDN11 may prevent cell migration and invasion by interfering with the microtubule polymerization dynamics. By contrast, in NPC cells, aberrant promoter hypermethylation impairs GATA binding and causes transcriptional silencing of CLDN11. In the absence of CLDN11, microtubules undergo rapid polymerization, in turn promoting basement membrane breakdown, motility, invasiveness, plasticity, and cell cycle, thus contributing to a more cancerous phenotype of NPC cells. The tubulin polymerization inhibitor nocodazole can serve as a therapeutic drug to block migration in NPC