For example, collagen prolyl 4-hydroxylases (P4Hs), essential enzymes in the synthesis of collagens and collagen lysyl hydroxylases (PLOD2) required for ECM stiffness, are induced in cancer cells by exposure to hypoxia, which is dependent on HIF-1α, but not HIF-2α [48,49]. The gene discussed is PLOD2; the disease is cancer.