Further supporting a relationship between estrogens and HIF-1α, our previous studies have demonstrated that estrogenic GPER signaling triggers VEGF expression by upregulating HIF-1α in normoxic breast cancer cells, cancer-associated fibroblasts (CAFs), and mouse xenografts of breast cancer, leading to neoangiogenesis and enhanced tumor growth [155]. The gene discussed is GPER1; the disease is cancer.