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Claudins: the newly emerging targets in breast cancer

Published:September 08, 2022DOI:https://doi.org/10.1016/j.clbc.2022.09.001

      Article highlights

      • Claudins are the family of proteins that form the backbone of tight junctions that connect the apices of adjacent cells and maintain cell polarity.
      • Dysregulation in structure, function, or localization of claudins in tight junctions is linked with various human diseases, including malignancies.
      • Different molecular subtypes of breast cancer show differential claudin expression. An upregulated expression of claudins 7, 8 and claudins 1, 4 has been noted in luminal and basal-like subtypes, respectively.
      • Recent studies have just started to unravel the extensive impact of claudins on the behavior and properties of different breast cancer subtypes.
      • Both over and underexpression of claudins is implicated in tumor progression (high claudin 4 in TNBCs, low claudin 16), metastasis (high claudin 2 in liver metastases, low claudins 7 and 12), chemoresistance (claudins 6 and 4), and stemness (claudins 3, 4, and 7) in breast malignancies.
      • Antibodies targeting claudins 1, 3, and 4 have been investigated in some malignancies like pancreatic cancer.
      • Therefore, claudins can act as the leading therapeutic targets in the context of malignancies like breast cancer in the future.

      Abstract

      Introduction

      Claudin-low breast cancers are recently described entities showing low expression of certain claudins and cell adhesion molecules. Claudins constitute the backbone of tight junctions (TJs) formed between two cells. Their dysregulation plays a vital role in tumorigenesis.

      Areas covered

      First part of the article focuses on the role of claudins in the TJ organization, their structural-functional characteristics, and post-transcriptional and translational modifications. The latter part of the review attempts to summarize existing knowledge regarding the status of claudins in breast cancer. The article also provides an overview of the effect of claudins on tumor progression, metastasis, stemness, chemotherapy resistance, and their crosstalk with relevant signaling pathways in breast cancer.

      Conclusion

      Claudins can act as two-edged swords in tumors. Some claudins have either tumor-suppressive/promoting action, while others work as both in a context-dependent manner. Claudins regulate many important events in breast cancer. However, the intricacies involved in their activity are poorly understood. Post-translational modifications in claudins and their impact on TJ integrity, function, and tumor behavior are still unclear. Although their role in adverse events in breast cancer is recognized, their potential to serve as relevant targets for future therapeutics, especially for difficult-to-treat subtypes of the above malignancy, remains to be explored.

      Graphical abstract

      Keywords

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