YAP, a mammalian ortholog of Drosophila Yorkie (Yki), is a candidate oncogene located in a 350-kb amplicon on mouse chromosome 9, syntenic to the 11q22 amplicon in human cancers. This amplicon contains only the YAP gene, unlike the larger human amplicon, which includes multiple genes. Overexpression of YAP in human nontransformed mammary epithelial cells induces epithelial-to-mesenchymal transition (EMT), suppression of apoptosis, growth factor-independent proliferation, and anchorage-independent growth in soft agar, suggesting a potential oncogenic role for YAP in 11q22-amplified human cancers. YAP functions as a transcriptional coactivator, activating proliferation by inducing cyclin E expression and inhibiting apoptosis by inducing DIAP1. The Hippo (Hpo)-Salvador (Sav)-Warts (Wts) signaling pathway negatively regulates these activities. In mouse models, YAP overexpression leads to EMT, invasive morphology, and increased migration in mammary epithelial cells. YAP also promotes EGF-independent proliferation and inhibits apoptosis in both MCF10A and HMECtert cells. These findings suggest that YAP contributes to malignant transformation in cancers harboring the 11q22 amplicon and highlight the potential significance of the Hippo pathway in human cancer. YAP's oncogenic activity is conserved in mammals, and its role in tumor development is supported by studies in mouse models. The study also highlights the importance of the Hippo pathway in regulating proliferation and apoptosis in mammalian cells. YAP's function as an oncogene is further supported by its ability to induce anchorage-independent growth in soft agar, a hallmark of tumorigenicity. The study underscores the potential of YAP as a key driver in the 11q22 amplicon and its role in the Hippo signaling pathway.YAP, a mammalian ortholog of Drosophila Yorkie (Yki), is a candidate oncogene located in a 350-kb amplicon on mouse chromosome 9, syntenic to the 11q22 amplicon in human cancers. This amplicon contains only the YAP gene, unlike the larger human amplicon, which includes multiple genes. Overexpression of YAP in human nontransformed mammary epithelial cells induces epithelial-to-mesenchymal transition (EMT), suppression of apoptosis, growth factor-independent proliferation, and anchorage-independent growth in soft agar, suggesting a potential oncogenic role for YAP in 11q22-amplified human cancers. YAP functions as a transcriptional coactivator, activating proliferation by inducing cyclin E expression and inhibiting apoptosis by inducing DIAP1. The Hippo (Hpo)-Salvador (Sav)-Warts (Wts) signaling pathway negatively regulates these activities. In mouse models, YAP overexpression leads to EMT, invasive morphology, and increased migration in mammary epithelial cells. YAP also promotes EGF-independent proliferation and inhibits apoptosis in both MCF10A and HMECtert cells. These findings suggest that YAP contributes to malignant transformation in cancers harboring the 11q22 amplicon and highlight the potential significance of the Hippo pathway in human cancer. YAP's oncogenic activity is conserved in mammals, and its role in tumor development is supported by studies in mouse models. The study also highlights the importance of the Hippo pathway in regulating proliferation and apoptosis in mammalian cells. YAP's function as an oncogene is further supported by its ability to induce anchorage-independent growth in soft agar, a hallmark of tumorigenicity. The study underscores the potential of YAP as a key driver in the 11q22 amplicon and its role in the Hippo signaling pathway.