The study investigates the role of epithelial to mesenchymal transition (EMT) in lung metastasis and chemoresistance in breast cancer. Using a lineage tracing system, the researchers found that within primary tumors, a small portion of tumor cells undergo EMT, but lung metastases primarily consist of non-EMT tumor cells maintaining their epithelial phenotype. Inhibiting EMT by overexpressing miR-200 did not affect lung metastasis development. However, EMT cells significantly contribute to recurrent lung metastasis formation after chemotherapy, as they survive cyclophosphamide treatment due to reduced proliferation, apoptotic tolerance, and elevated expression of chemoresistance-related genes. Overexpression of miR-200 abrogated this resistance. The study suggests that targeting EMT may be a potential strategy to enhance the effectiveness of conventional chemotherapies in breast cancer treatment.The study investigates the role of epithelial to mesenchymal transition (EMT) in lung metastasis and chemoresistance in breast cancer. Using a lineage tracing system, the researchers found that within primary tumors, a small portion of tumor cells undergo EMT, but lung metastases primarily consist of non-EMT tumor cells maintaining their epithelial phenotype. Inhibiting EMT by overexpressing miR-200 did not affect lung metastasis development. However, EMT cells significantly contribute to recurrent lung metastasis formation after chemotherapy, as they survive cyclophosphamide treatment due to reduced proliferation, apoptotic tolerance, and elevated expression of chemoresistance-related genes. Overexpression of miR-200 abrogated this resistance. The study suggests that targeting EMT may be a potential strategy to enhance the effectiveness of conventional chemotherapies in breast cancer treatment.