PERK activation and its downstream signaling have been shown to be mandatory for hypoxic adaptation of different cancer and noncancer cell lines through upregulation of ROS defense pathways and glutamine metabolism.25 To assess whether depletion or chemical inhibition of PDI impairs this adaptation processes similar to PERK blockade, proliferation was examined when the cells were cultured under hypoxic conditions (1% O2). The gene discussed is EIF2AK3; the disease is cancer.