PDI chaperones and client proteins in cancer pathogenesis

Secretory proteins are folded in the ER by chaperones, some of which belong to the Protein Disulfide Isomerase (PDI) family. Unfolded secretory proteins are generally retained and/or degraded by the ER associated degradation (ERAD) pathway. The function of ER chaperones, which themselves may be regulated by oxidative stress and altered Ca²⁺ homeostasis, can also determine the cell’s responsiveness toward oxidative stress, including its sensitivity to apoptosis. Inhibiting PDI chaperone activity might therefore cause various disease-related secretory proteins to be retained and degraded, thereby reducing disease severity.