The understanding of the overall role exerted by GPER in this neoplasia has become rather complex, considering the strong evidence of its ability to mediate the estrogen stimulation of main components of the tumor microenvironment, such as CAFs (De Francesco et al., 2014; Madeo and Maggiolini, 2010; Pupo et al., 2013, , 2014; Vivacqua et al., 2015). This evidence concerns the gene GPER1 and neoplasm.