This study investigates the role of YAP, a gene located on chromosome 11q22, in tumorigenesis. YAP, which encodes the mammalian ortholog of Drosophila Yorkie (Yrk), is a downstream effector of the Hippo-Hippo kinase (Hpo)-Salvador (Sav)-Warts (Wts) signaling cascade, known to regulate cellular proliferation and apoptosis. In mouse mammary tumors, a small 350-kb amplicon containing YAP was identified. Overexpression of YAP in human nontransformed mammary epithelial cells (MCF10A) induced epithelial-to-mesenchymal transition (EMT), suppressed apoptosis, promoted growth factor-independent proliferation, and supported anchorage-independent growth in soft agar. These findings suggest that YAP contributes to malignant transformation in cancers with the 11q22 amplicon and highlight the potential significance of this pathway in human cancer. The study also discusses the conservation of the Yki-regulating pathway between Drosophila and mammalian cells, and the diverse functions of YAP in mammalian cells.This study investigates the role of YAP, a gene located on chromosome 11q22, in tumorigenesis. YAP, which encodes the mammalian ortholog of Drosophila Yorkie (Yrk), is a downstream effector of the Hippo-Hippo kinase (Hpo)-Salvador (Sav)-Warts (Wts) signaling cascade, known to regulate cellular proliferation and apoptosis. In mouse mammary tumors, a small 350-kb amplicon containing YAP was identified. Overexpression of YAP in human nontransformed mammary epithelial cells (MCF10A) induced epithelial-to-mesenchymal transition (EMT), suppressed apoptosis, promoted growth factor-independent proliferation, and supported anchorage-independent growth in soft agar. These findings suggest that YAP contributes to malignant transformation in cancers with the 11q22 amplicon and highlight the potential significance of this pathway in human cancer. The study also discusses the conservation of the Yki-regulating pathway between Drosophila and mammalian cells, and the diverse functions of YAP in mammalian cells.