Emerging Roles of Claudins in Human Cancer
Open Access
- 4 September 2013
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 14 (9), 18148-18180
- https://doi.org/10.3390/ijms140918148
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
This publication has 132 references indexed in Scilit:
- Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancerOncogenesis, 2012
- Claudin 6: a novel surface marker for characterizing mouse pluripotent stem cellsCell Research, 2012
- Claudin-7 inhibits human lung cancer cell migration and invasion through ERK/MAPK signaling pathwayExperimental Cell Research, 2011
- Eradication of chemotherapy‐resistant CD44+ human ovarian cancer stem cells in mice by intraperitoneal administration of clostridium perfringens enterotoxinCancer, 2011
- Primary ex vivo cultures of human fallopian tube epithelium as a model for serous ovarian carcinogenesisOncogene, 2009
- HDAC inhibitors regulate claudin-1 expression in colon cancer cells through modulation of mRNA stabilityOncogene, 2009
- Phosphorylation of claudin-4 by PKCε regulates tight junction barrier function in ovarian cancer cellsExperimental Cell Research, 2007
- Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapyBritish Journal of Cancer, 2005
- Molecular mechanisms of drug resistanceThe Journal of Pathology, 2005
- Signalling to and from tight junctionsNature Reviews Molecular Cell Biology, 2003