GPER mediates estrogen-stimulated activation of ERK and PI3K via matrix metalloproteinase activation and subsequent EGFR transactivation (Figure 2), and thus ER-targeted medicinal drugs act as GPER agonists in this regard, and pharmacological inhibition of GPER activity may inhibit estrogen-mediated endometrial tumor growth [77]. This evidence concerns the gene GPER1 and endometrium neoplasm.