Claudin-4 as therapeutic target in cancer

BackgroundIntercellular junctional complexes such as adherens junctions and tight junctions are critical regulators of cellular polarity, paracellular permeability and metabolic and structural integrity of cellular networks. Abundant expression analysis data have yielded insights into the complex pattern of differentially expressed cell-adhesion proteins in epithelial cancers and provide a useful platform for functional, preclinical and clinical evaluation of novel targets.Scope of reviewThis review will focus on the role of claudin-4, an integral constituent of tight junctions, in the pathophysiology of epithelial malignancies with particular focus pancreatic cancer, and its potential applicability for prognostic, diagnostic and therapeutic approaches.Major conclusionsClaudin-4 expression is widely dysregulated in epithelial malignancies and in a number of premalignant precursor lesions. Although the functional implications are only starting to unravel, claudin-4 seems to play an important role in tumour cell invasion and metastasis, and its dual role as receptor of Clostridium perfringens enterotoxin (CPE) opens exciting avenues for molecular targeted approaches.General significanceClaudin-4 constitutes a promising molecular marker for prognosis, diagnosis and therapy of epithelial malignancies.

► Claudin-4 is an integral constituent of tight junctions.
► Claudin-4 is differentially expressed in a variety of epithelial malignancies.
► Claudin-4 constitutes the receptor of Clostridium perfringens enterotoxin.
► Epigenetic modifications may be critical for claudin-4 deregulation.
► Claudin-4 opens novel avenues for molecular diagnostics and therapeutics in cancer.