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
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 2 cells. Their dysregulation plays a vital
role in tumorigenesis. 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. Claudins can act as 2-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
Published online: September 08, 2022
Accepted:
September 4,
2022
Received:
August 13,
2022
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© 2022 Elsevier Inc. All rights reserved.
