Roles of Protein Disulfide Isomerase in Breast Cancer

Simple Summary Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and has a poor prognosis and higher recurrence rate due to ineffective therapy. Even with newly approved therapeutics, only limited TNBC patients could have benefited from the regimens. Protein disulfide isomerase (PDI) has been of great interest as a potential therapeutic target for cancers due to its impacts on tumor progression, metastasis, and clinical outcomes. Here, we discuss the roles of PDI members in breast cancers such as TNBC and the PDI inhibitors studied in breast cancer research. Protein disulfide isomerase (PDI) is the endoplasmic reticulum (ER)'s most abundant and essential enzyme and serves as the primary catalyst for protein folding. Due to its apparent role in supporting the rapid proliferation of cancer cells, the selective blockade of PDI results in apoptosis through sustained activation of UPR pathways. The functions of PDI, especially in cancers, have been extensively studied over a decade, and recent research has explored the use of PDI inhibitors in the treatment of cancers but with focus areas of other cancers, such as brain or ovarian cancer. In this review, we discuss the roles of PDI members in breast cancer and PDI inhibitors used in breast cancer research. Additionally, a few PDI members may be suggested as potential molecular targets for highly metastatic breast cancers, such as TNBC, that require more attention in future research.