TJs are large intercellular adhesion complexes that maintain cell polarity in normal epithelia and endothelia. During the metastatic process, TJs must be ‘loosened’ or dismantled in cancer cells to enable migration and dissemination. Diminished TJ integrity must also occur within endothelial cells to allow intravasation and extravasation of cancer cells across endothelial barriers. Claudins are critical components of TJs, forming homo- and heteromeric interactions between the adjacent cells, which have been implicated as key modulators of carcinogenesis and metastasis. Numerous epithelial-derived cancers display altered claudin expression patterns and certain claudins can now be used as biomarkers to predict patient prognosis. Moreover, claudins have been functionally implicated in numerous steps of the metastatic cascade. The distinct roles played by claudins during the cancer progression to metastatic disease are just starting to be elucidated. A more complete understanding of the mechanisms through which claudins augment cancer metastasis is required to develop new therapeutic agents against this family of proteins. In this review, we will summarize the relationship between the claudin expression and clinical outcomes in diverse cancers, discuss tumor intrinisic roles through which claudins regulate metastasis and explore claudin-mediated functions within stromal cells that influence the metastatic process. Finally, we will consider possible strategies for targeting claudins that have the potential to improve the management of metastatic cancer.
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We thank members of the Siegel laboratory for their thoughtful comments on the manuscript. Research conducted in the author’s laboratory was supported by grants from the CIHR (MOP-136907 to PMS). PMS is a William Dawson Scholar of McGill University.
The authors declare no conflict of interest.
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Tabariès, S., Siegel, P. The role of claudins in cancer metastasis. Oncogene 36, 1176–1190 (2017). https://doi.org/10.1038/onc.2016.289