The G-protein-coupled oestrogen receptor (GPER), distinct from nuclear ER, also plays a role in oestrogen-dependent development and progression of cancers, including RCC.107, , –110 RCC cell lines express GPER abundantly and its activation promotes RCC cell migration and invasion by upregulating matrix metalloproteinase-2 (MMP-2) and MMP-9, as well as activating downstream signalling pathways, particularly MAPK and PI3K/AKT, promoting cell migration via the PI3K/AKT/MMP-9 pathway.66 This evidence concerns the gene AKT1 and cancer.