Claudin-4 is part of the
Claudin family of transmembrane tight junction (TJ)
proteins found in almost all tissues and, together with adherens junctions and desmosomes, forms epithelial and endothelial junctional complexes. Although the distribution of
Claudin-4 occurs in many cell types, the level of expression is cell-specific.
Claudin proteins regulate cell proliferation and differentiation by binding cell-signaling
ligands, and its expression is upregulated in several
cancers. As a result, alterations in
Claudin expression patterns or distribution are vital in the pathology of
cancer. Profiling the genetic expression of
Claudin-4 showed that
Claudin-4 is also a receptor for the
clostridium perfringens enterotoxin (CPE) and that
Claudin-4 has a high sequence similarity with CPE's high-affinity receptor. CPE is cytolytic due to its ability to form pores in cellular membranes, and CPE treatment in
breast cancer cells have shown promising results due to the high expression of
Claudin-4. The C-terminal fragment of
CPE (c-CPE) provides a less toxic alternative for
drug delivery into
breast cancer cells, particularly metastatic
tumors in the brain, especially as
Claudin-4 expression in the central nervous system (CNS) is low. Therefore, c-CPE provides a unique avenue for the treatment of breast-brain metastatic
tumors.