Claudins are major
integral membrane proteins of tight junctions. Altered expression of several
claudin proteins, in particular
claudin-1, -3, -4 and -7, has been linked to the development of various
cancers. Although their dysregulation in
cancer suggests that
claudins play a role in
tumorigenesis, the exact underlying mechanism remains unclear. The involvement of
claudins in
tumor progression was suggested by their important role in the migration, invasion and
metastasis of
cancer cells in a tissue-dependent manner. Recent studies have shown that they play a role in epithelial to mesenchymal transition (EMT), the formation of cancer stem cells or tumor-initiating cells (CSCs/
TICs), and chemoresistance, suggesting that
claudins are promising targets for the treatment of chemoresistant and recurrent
tumors. A recently identified
claudin-low
breast cancer subtype that is characterized by the enrichment of EMT and stem cell-like features is significantly associated with disease recurrence, underscoring the importance of
claudins as predictors of
tumor recurrence. The critical role of epigenetic mechanisms in the regulation of
claudin expression indicates the possible application of epigenetic
therapy to target
claudins. A better understanding of the emerging role of
claudins in CSC/
TICs and chemoresistance may help to develop
therapies against recurrent
cancers.