AKT1 and breast cancer: Interestingly, we identified not only some known signaling pathways previously reported in tamoxifen-resistant breast cancer including Wnt signaling, TGF-beta and PI3K-Akt signaling [32, 33, 38, 45], but also a few novel 3D spheroid-specific pathways such as Hippo and Rap1 signaling pathways, as well as a upstream pathway regulating Hippo signaling: G Protein pathways (Fig. 4C).