Claudins: emerging targets for cancer therapy.
The claudin (CLDN) family of transmembrane proteins plays a critical role in the maintenance of epithelial and endothelial tight junctions. In addition to their function in preserving the structure of tight junctions, CLDNs might also play a role in the maintenance of the cytoskeleton and in cell signalling. Interestingly, several studies have recently reported specific CLDN family members to be overexpressed in a wide variety of cancer types. Although their functional role in cancer progression remains unclear, the differential expression of these proteins between tumour and normal cells, in addition to their membrane localisation, makes them prime candidates for cancer therapy. Preclinical studies have shown that tumour cells overexpressing CLDNs can be successfully targeted via several approaches, including the use of anti-CLDN antibodies as well as the cytolytic enterotoxin from Clostridium perfringens. Further studies are needed to determine the potential systemic toxicity of this approach considering the ubiquitous expression of CLDNs in the body, but CLDN-targeted therapeutics appear to have promise in the treatment of cancer.
Kominsky
Scott L
SL
Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, 720 Rutland Ave, Baltimore, MD 21205, USA. kominsc@jhmi.edu
D020816:Amino Acid Motifs; D062445:Claudin-1; D003016:Clostridium perfringens / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011487:Protein Conformation; D019108:Tight Junctions / Q000378:metabolism; D014018:Tissue Distribution
D062445:Claudin-1; D008565:Membrane Proteins