In the same family, acting on the endothelin type A (ETA) or type B (ETB) receptor, the small peptide endothelin-1 (ET-1), recognized as a critical regulator of different human cancers (Rosanò et al., 2013), provides a signal input for shaping invasive protrusions with efficient matrix degradation during cancer invasion and metastases. This evidence concerns the gene EDN1 and cancer.