This study demonstrates that breast cancer stem cells (CSCs) can be generated through epithelial-mesenchymal transition (EMT) in human mammary epithelial cells. The researchers used a model of mammary tumor progression to show that cells with stem and tumorigenic properties can be derived from normal mammary epithelial cells after activation of the Ras-MAPK pathway. The acquisition of these properties is driven by EMT induction. The study shows that CD44⁺CD24⁻/low cells, which are associated with stem-like properties, can be generated from CD44⁺CD24⁺ non-tumorigenic mammary epithelial cells through activation of the Ras/MAPK signaling pathway and EMT induction. These cells are highly tumorigenic when injected into immunocompromised mice and share features of normal stem cells, including self-renewal and the ability to generate heterogeneous progeny. The study also shows that the transformation of mammary epithelial cells into cancer cells is associated with EMT, which is characterized by the loss of epithelial markers and the gain of mesenchymal markers. The researchers found that the introduction of oncogenes such as H-RasV12 and K-RasV12 leads to the emergence of CD44⁺CD24⁻/low cells, which are associated with EMT. The addition of TGFβ1, a potent inducer of EMT, significantly accelerates the emergence of CD44⁺CD24⁻/low cells. The study suggests that EMT is a crucial process in the generation of breast cancer stem cells and that the CD44⁺CD24⁻/low cells may reflect the propensity of malignant cells to undergo transdifferentiation and metastasize. The findings support the hypothesis that EMT is involved in the progression of breast cancer and that the gene-expression signature of CD44⁺CD24⁻/low cells is associated with the prognosis of breast cancer. The study also highlights the role of the Ras/MAPK pathway and TGFβ in the induction of EMT and the generation of breast cancer stem cells.This study demonstrates that breast cancer stem cells (CSCs) can be generated through epithelial-mesenchymal transition (EMT) in human mammary epithelial cells. The researchers used a model of mammary tumor progression to show that cells with stem and tumorigenic properties can be derived from normal mammary epithelial cells after activation of the Ras-MAPK pathway. The acquisition of these properties is driven by EMT induction. The study shows that CD44⁺CD24⁻/low cells, which are associated with stem-like properties, can be generated from CD44⁺CD24⁺ non-tumorigenic mammary epithelial cells through activation of the Ras/MAPK signaling pathway and EMT induction. These cells are highly tumorigenic when injected into immunocompromised mice and share features of normal stem cells, including self-renewal and the ability to generate heterogeneous progeny. The study also shows that the transformation of mammary epithelial cells into cancer cells is associated with EMT, which is characterized by the loss of epithelial markers and the gain of mesenchymal markers. The researchers found that the introduction of oncogenes such as H-RasV12 and K-RasV12 leads to the emergence of CD44⁺CD24⁻/low cells, which are associated with EMT. The addition of TGFβ1, a potent inducer of EMT, significantly accelerates the emergence of CD44⁺CD24⁻/low cells. The study suggests that EMT is a crucial process in the generation of breast cancer stem cells and that the CD44⁺CD24⁻/low cells may reflect the propensity of malignant cells to undergo transdifferentiation and metastasize. The findings support the hypothesis that EMT is involved in the progression of breast cancer and that the gene-expression signature of CD44⁺CD24⁻/low cells is associated with the prognosis of breast cancer. The study also highlights the role of the Ras/MAPK pathway and TGFβ in the induction of EMT and the generation of breast cancer stem cells.