Py2T long term cells and mesenchymal breast cancer cells (MTΔECad) treated with different inhibitors. Py2T long term cells and mesenchymal breast cancer cells (MTΔECad) treated with different inhibitors

Cancer cell plasticity facilitates the development of therapy resistance and malignant progression. De-differentiation processes, such as an epithelial-mesenchymal transition (EMT), are known to enhance cellular plasticity. Here, we demonstrate that cancer cell plasticity can be exploited therapeutically by forcing the trans-differentiation of EMT-derived breast cancer cells into post-mitotic and functional adipocytes. Delineation of the molecular pathways underlying such trans-differentiation has motivated a combination therapy with a MEK inhibitor and the anti-diabetic drug Rosiglitazone in various mouse models of murine and human breast cancer in vivo. This combination therapy provokes the conversion of invasive and disseminating cancer cells into post-mitotic adipocytes leading to the repression of primary tumor invasion and metastasis formation Overall design: Py2T long term cells and mesenchymal breast cancer cells (MTΔECad) were harvested at day7 and treated with different inhibitors (two biological replicates per time-point)