Time course of mesenchymal breast cancer cells (MT?ECad) undergoing transdifferentiation into terminally differentiated adipocytes

A high degree of cell plasticity seems to promote malignant tumour progression, and an epithelial-mesenchymal transition (EMT) is suspected to provide cancer cells with increased cell plasticity for the development of metastasis and therapy resistance. Here, we have tested whether the EMT-induced cancer cell plasticity can be therapeutically exploited and we report the efficient conversion of breast cancer cells, which have undergone an EMT, into post-mitotic adipocytes. Delineation of the molecular pathways underlying such transdifferentiation has motivated a combination therapy with a MEK inhibitor and Rosiglitazone to demonstrate the conversion of invasive cancer cells into adipocytes and the repression of primary tumor invasion and metastasis formation in mouse models of breast cancer. The results indicate the high potential to utilize the increased cell plasticity of invasive cancer cells for differentiation therapy and they raise the possibility to employ pharmacological treatments to interfere with tumor invasion and metastasis. Overall design: Mesenchymal breast cancer cells (MT?ECad) were harvested at six different time-points during trasndifferentiation into terminally differentiated adipocytes (two biological replicates per time-point)

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Ishay-Ronen D, Diepenbruck M, Kalathur RKR, Sugiyama N, Tiede S, Ivanek R, Bantug G, Morini MF, Wang J, Hess C, Christofori G