ERN1 and neoplasm: Cell treated by specific inhibitors of the UPR downstream mediators or mice malignant cells lacking IRE1α, XBP-1, PERK, or ATF6 are more sensitive to hypoxia, with higher production of ROS, lower angiogenesis, delayed tumour progression and metastasis [139,154,155,156,157,158,159,160,161,162,163].