Abstract
Why are many metastases differentiated? Invading and disseminating carcinoma cells can undergo an epithelial–mesenchymal transition (EMT), which is associated with a gain of stem cell-like behaviour. Therefore, EMT has been linked to the cancer stem cell concept. However, it is a matter of debate how subsequent mesenchymal–epithelial transition (MET) fits into the metastatic process and whether a MET is essential. In this Opinion article, I propose two principle types of metastatic progression: phenotypic plasticity involving transient EMT–MET processes and intrinsic genetic alterations keeping cells in an EMT and stemness state. This simplified classification integrates clinically relevant aspects of dormancy, metastatic tropism and therapy resistance, and implies perspectives on treatment strategies against metastasis.
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Acknowledgements
The author apologizes to those authors whose work could not be cited directly owing to space constraints. For stimulating discussions and critical reading of the manuscript the author is very grateful to S. Brabletz and M. Swierk. T.B. is supported by the DFG (no. BR 1399/6-1 and the SFB 850, B2), the Deutsche Krebshilfe (grant no. 109430), the Speman Graduate School of Biology and Medicine (SGBM) and the BIOSS Centre for Biological Signalling Studies.
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Brabletz, T. To differentiate or not — routes towards metastasis. Nat Rev Cancer 12, 425–436 (2012). https://doi.org/10.1038/nrc3265
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DOI: https://doi.org/10.1038/nrc3265
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