Mechanistically, we demonstrated that 1) MCs express both ETA and ETB receptors, along with β-arr1, and secrete ET-1; 2) An autocrine/paracrine ET-1 loop drives p42/44MAPK and NF-kB pathways supporting cell proliferation; 3) ET-1 receptors/β-arr1 activation elicits an MMT program, triggering the enhanced secretion of cancer-related proteins, MC migration and invasion, and SOC cell transmesothelial migration; 4) In SOC peritoneal specimens, ET-1 receptors co-localize with MMT markers. The gene discussed is EDN1; the disease is cancer.