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
Graphical Abstract
Keywords
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Article Info
Publication History
Accepted:
September 4,
2022
Received:
August 13,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
