Previous research has indicated that ET-1 can suppress osteoblast apoptosis by stimulating the calcineurin/NFAT pathway.187 This process may also involve E-cadherin augmentation, which correlates with tumor cell adhesion, as well as upregulated Runx2 activity and SPARC expression, which is related to osteomimicry.188,189 The inductive effect of ET-1 on IL-18 expression has been identified in osteoblasts at the gene promoter/transcriptional level through a p38 MAPK-dependent pathway.190 IL-18, as discussed above, acts as a regulator of osteoblast proliferation. The gene discussed is IL18; the disease is neoplasm.