Claudin 1: An Emerging Target for Triple-Negative Breast Cancer

Claudin 1 is a transmembrane protein known as a key component of the tight junctions playing a pivotal role in cell-cell interaction and homeostasis of epithelial cells. In breast cancer, the expression of claudin 1 is absent or strongly diminished in 76% of triple-negative breast cancer (TNBC). These tumors constitute the most aggressive subtype of breast cancer. They are a heterogeneous group of breast tumors that do not express estrogen receptor (ER) α, progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Therefore, TNBC patients are not eligible for targeted therapies that have been developed for other breast cancer subtypes. TNBCs have a higher tendency to form metastasis and they rapidly acquire chemo-resistance. Therefore, TNBCs represent a major challenge in cancerology, and the main goal of cancer research is to characterize potential specific targets to treat these tumors lacking efficient therapies. Clinical studies reported that a loss of claudin 1 expression correlates with increased aggressiveness and metastasis potential associated with recurrence of disease in invasive breast carcinoma patients. Although the role of claudin 1 in breast cancer is not clearly defined, several in vitro studies suggested that claudin 1 functions as a tumor suppressor. The reexpression of claudin 1 in some TNBC cell line was shown to be sufficient to induce apoptosis, suggesting that claudin 1 expression could constitute a new therapeutic option in “claudin 1–low” TNBC. This review summarizes the role of claudin 1 in TNBC cancer and its impact on developing novel strategies to treat breast cancer.