Silencing Esr1 in Esr1+/Grpr+ melanoma reduced Grpr mRNA, whereas Esr1 overexpression increased it (Fig. 5f,g and Extended Data Fig. 7f,g), confirming that Esr1 regulates Grpr. In Ecad-expressing melanoma, CDH1 silencing in mouse and human cells raised ESR1 and GRPR mRNA (Fig. 5h and Extended Data Fig. 7h), supporting the inverse correlation between CDH1 and GRPR seen in TCGA data (Fig. 2j). This evidence concerns the gene GRPR and melanoma.