For instance, HIF-1α was shown to be required for the up-regulation of GPER by hypoxia and both HIF-1α and GPER triggered the up-regulation of the vascular endothelial growth factor (VEGF) in breast cancer cells and main components of the tumor microenvironment, as cancer-associated fibroblasts (CAFs) [13]. This evidence concerns the gene GPER1 and neoplasm.