On the basis of these studies we propose that a signaling network between HIF-1α, GPER, and Notch, initiated by either HIF-1α in hypoxic cancer cell or E2/GPER in normoxic cancer cells, may account for Notch-dependent induction of Snail, a key transcriptional repressor of E-cadherin in breast cancer EMT. This evidence concerns the gene CDH1 and breast carcinoma.