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Emerging Roles of Claudins in Human Cancer
College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Korea
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Korea
Received: 12 August 2013; in revised form: 23 August 2013 / Accepted: 27 August 2013 / Published: 4 September 2013
Abstract: Claudins are major integral membrane proteins of tight junctions. Altered expression of several claudin proteins, in particular claudin-1, -3, -4 and -7, has been linked to the development of various cancers. Although their dysregulation in cancer suggests that claudins play a role in tumorigenesis, the exact underlying mechanism remains unclear. The involvement of claudins in tumor progression was suggested by their important role in the migration, invasion and metastasis of cancer cells in a tissue-dependent manner. Recent studies have shown that they play a role in epithelial to mesenchymal transition (EMT), the formation of cancer stem cells or tumor-initiating cells (CSCs/TICs), and chemoresistance, suggesting that claudins are promising targets for the treatment of chemoresistant and recurrent tumors. A recently identified claudin-low breast cancer subtype that is characterized by the enrichment of EMT and stem cell-like features is significantly associated with disease recurrence, underscoring the importance of claudins as predictors of tumor recurrence. The critical role of epigenetic mechanisms in the regulation of claudin expression indicates the possible application of epigenetic therapy to target claudins. A better understanding of the emerging role of claudins in CSC/TICs and chemoresistance may help to develop therapies against recurrent cancers.
Keywords: claudin; cancer; epithelial to mesenchymal transition (EMT); cancer stem cells or tumor-initiating cells (CSC/TICs); chemoresistance; tumor recurrence; epigenetic regulation
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Kwon, M.J. Emerging Roles of Claudins in Human Cancer. Int. J. Mol. Sci. 2013, 14, 18148-18180.
Kwon MJ. Emerging Roles of Claudins in Human Cancer. International Journal of Molecular Sciences. 2013; 14(9):18148-18180.
Kwon, Mi J. 2013. "Emerging Roles of Claudins in Human Cancer." Int. J. Mol. Sci. 14, no. 9: 18148-18180.