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Cancer Cell. 2019 Jan 14;35(1):17-32.e6. doi: 10.1016/j.ccell.2018.12.002.

Gain Fat-Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis.

Author information

1
Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland. Electronic address: pandanaro@gmail.com.
2
Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.
3
University Hospital Basel, Department of Biomedicine, University of Basel, Switzerland.
4
Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland. Electronic address: gerhard.christofori@unibas.ch.

Abstract

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 MEK inhibitors 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.

KEYWORDS:

EMT; TGFβ-signaling; adipocyte; adipogenesis; breast cancer; cell plasticity; differentiation therapy; invasion; metastasis; trans-differentiation

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