Protein disulfide isomerases regulate androgen receptor stability and promote prostate cancer cell growth and survival

In this study, we identified the protein disulfide isomerase (PDI) enzymes PDIA1 and PDIA5 as critical mediators of prostate cancer cell growth and survival. Our research demonstrated that these enzymes have a multifaceted role in prostate cancer: they protect cells from oxidative stress, maintain mitochondrial function, and have important functions as regulators of androgen receptor (AR), a critical oncogenic driver. Indeed, targeting PDIA1/PDIA5 causes destabilization of AR protein, and combining PDI inhibitors with AR-targeting drugs boosted antitumor responses. This work positions PDIA1/PDIA5 as viable therapeutic targets.