 \[[@B22-cancers-05-01163]\]. For the biosynthesis and the function of many proteins, disulfide bonds are crucial. They promote structural stability, facilitate the assembly of multi-protein complexes and can modulate redox-dependent functions in response to changes in the cell. Disulfide bonds can also mediate the formation of productive folding intermediates and have been shown in the ER to promote thiol-mediated protein retention \[[@B22-cancers-05-01163]\].

ER stress can be provoked through a variety of physiological conditions, including perturbations in calcium bhomeostasis, glucose/energy deprivation, redox changes, ischemia, hyperhomocystinemia, viral infections and mutations that impair client protein folding \[[@B23-cancers-05-01163]\]. Likewise, an inadequate supply of glucose affects protein glycosylation and the production of ATP, both of which could lead to the accumulation of unfolded proteins in the ER, resulting in ER stress. Elevated ER stress and increased chaperone protein expression have been correlated with tumor initiation, malignancy and metastasis \[[@B11-cancers-05-01163]\]. Cancer cells face an exceptionally harsh microenvironment during their growth, including hypoxia, nutrient deprivation, acidosis, and non-permissive interactions with stromal cells and extracellular matrix. During tumor development, several ER stress activators (hypoxia and low glucose) are also known to induce resistance to chemotherapy through processes that are suggestive of ER-dependent mechanisms \[[@B24-cancers-05-01163]\].

As a consequence of ER stress, the cell has evolved an adaptive, coordinated response to limit accumulation of unfolded proteins in the ER. This signaling pathway is termed the unfolded protein response (UPR) \[[@B25-cancers-05-01163]\]. The molecular chaperones and folding sensors in the ER include the glucose regulated proteins 78 (GRP78; also known as Immunoglobulin Binding protein---BiP) and 94 (GRP94), the lectins, calnexin and calreticulin, and the thiol-disulfide oxidoreductases, pr