Role of claudins in tumorigenesis

The family of more than 20 claudin (CLDN) proteins comprises one of the major structural elements within the apical tight junction apparatus, a dynamic cellular nexus for maintenance of a luminal barrier, paracellular transport, and signal transduction. Loss of normal tight junction functions constitutes a hallmark of human carcinomas. CLDN I may support tumor suppressive functions in tissues such as the brain, where dramatic loss of expression has been demonstrated in glioblastoma multiforme. The role(s) for CLDNs 3 and 4 in tumorigenesis is less clear. CLDN4 appears to be over-expressed in ovarian and pancreatic carcinomas, and this raises the possibility that a unique, potentially non-toxic cancer cell target may be developed through the design of enterotoxin analogues. Future goals include understanding the biochemical and physiological mechanisms that are perturbed as a consequence of CLDN alterations in the progression of solid tumors. (c) 2005 Elsevier B.V. All rights reserved.