Claudin-5 participates in the regulation of endothelial cell motility.
A key step in metastasis is the interaction and penetration of the vascular endothelium by cancer cells. Tight Junctions (TJ) are located between the cancer epithelial cells and between the endothelial cells functioning in an adhesive manner. They represent a critical barrier which the cancer cells must overcome in order to penetrate and initiate metastasis. Claudin-5 is a protein member of the Claudin family, a group of TJ proteins expressed in both endothelial and epithelial cells. This study examined in vitro the effect of altering levels of expression of Claudin-5 in HECV cells. Insertion of Claudin-5 gene in HECV cells resulted in cells that were significantly less motile and less adhesive to matrix (P < 0.001). These cells also exhibited a significant decreased in the angiogenic potential (P < 0.001). Results also revealed a link between Claudin-5 and cell motility. Furthermore, a possible link between Claudin-5 and N-WASP, and Claudin-5 and ROCK was demonstrated when interactions between these proteins were seen in the cell line. Moreover, followed by treatment of N-WASP inhibitor (Wiskostatin) and ROCK inhibitor (Y-27632), cell motility and angiogenic potential were assessed in response to the inhibitors. Results showed that the knockdown of Claudin-5 in HECV cells masked their response to both N-WASP and ROCK inhibitors. In conclusion, this study portrays a new and interesting role for Claudin-5 in cell motility involving the N-WASP and ROCK signalling cascade which is beyond the primarily role of Claudin-5 in keeping the cell barrier tight as it was originally reported.
University Department of Surgery, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
Astrid
A
Escudero-Esparza
Wen G
WG
Jiang
Tracey A
TA
Martin
D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D062507:Claudin-5; D057167:Claudins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D055785:Gene Knockdown Techniques; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D018919:Neovascularization, Physiologic / Q000235:genetics; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism / Q000502:physiology*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000037:antagonists & inhibitors / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
C107466:CLDN5 protein, human; D062507:Claudin-5; D057167:Claudins; C495771:WASL protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D017228:Hepatocyte Growth Factor; D054460:rho-Associated Kinases