Targeting Cancer Cell Metastasis by Converting Cancer Cells into Fat

Cancer is a systemic heterogeneous disease that can undergo several rounds of latency and activation. Malignant tumors evolve through dynamic responses to microenvironmental signals and development of resistance following therapeutic interventions. Cancer cell adaptation is required for cell survival during metastatic dissemination and outgrowth. Epithelial-mesenchymal transition (EMT) plays a major role in facilitating cell plasticity in cancer and allows cancer cells to escape chemotherapies and targeted therapies through dedifferentiation and signaling adaptation processes. In our recent study, we showed that breast cancer cells that have undergone EMT can be terminally differentiated into adipocytes using the PPARγ agonist rosiglitazone combined with the MEK inhibitor trametinib. The conversion of invasive cancer cells into adipocytes repressed primary tumor invasion and metastasis formation in mouse models of breast cancer. The transdifferentiated cancer cell-derived adipocytes were growth-arrested and lost their cellular plasticity. These results indicate the high potential of utilizing the increased cell plasticity inherent to invasive cancer cells for transdifferentiation therapy.