Single cell polarity in liquid phase facilitates tumour metastasis

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  • Anna Lorentzen
  • Paul F. Becker, Technische Universitat Munchen
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  • Jan Kosla, Technische Universitat Munchen, Academy of Sciences of the Czech, German Cancer Research Center, Heidelberg
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  • Massimo Saini, German Cancer Research Center, Heidelberg, Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) GGmbH
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  • Kathrin Weidele, Fraunhofer-Institut für Toxikologie und Experimentelle Medizin
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  • Paolo Ronchi, European Molecular Biology Laboratory Heidelberg
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  • Corinna Klein, Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) GGmbH
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  • Monika J. Wolf, University Hospital Zurich
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  • Felix Geist, German Cancer Research Center, Heidelberg, Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) GGmbH
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  • Bastian Seubert, Technische Universitat Munchen, German Cancer Research Center, Heidelberg
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  • Marc Ringelhan, Technische Universitat Munchen, Technische Universität München
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  • Daniela Mihic-Probst, University Hospital Zurich
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  • Knud Esser, Technische Universitat Munchen
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  • Marko Roblek, University of Zurich
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  • Felix Kuehne, Technische Universitat Munchen
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  • Gaia Bianco, Technische Universitat Munchen
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  • Tracy O'Connor, Technische Universitat Munchen, German Cancer Research Center, Heidelberg
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  • Quentin Müller, Technische Universität München
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  • Kathleen Schuck, Technische Universität München
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  • Sebastian Lange, Technische Universität München
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  • Daniel Hartmann, Technische Universität München
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  • Saskia Spaich, University Medical Centre Mannheim
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  • Olaf Groß, Technische Universität München
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  • Jochen Utikal, German Cancer Research Center, Heidelberg, University Medical Center Mannheim
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  • Sebastian Haferkamp, University Hospital Regensburg
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  • Martin R. Sprick, German Cancer Research Center, Heidelberg, Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) GGmbH
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  • Amruta Damle-Vartak, Leibnitz Research Cenrtre for Working Environment and Human Factors (IfADo)
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  • Alexander Hapfelmeier, Technische Universität München
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  • Norbert Hüser, Technische Universität München
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  • Ulrike Protzer, Technische Universitat Munchen
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  • Andreas Trumpp, German Cancer Research Center, Heidelberg, Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) GGmbH
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  • Dieter Saur, Technische Universität München, German Cancer Research Center, Heidelberg
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  • Nachiket Vartak, Leibnitz Research Cenrtre for Working Environment and Human Factors (IfADo)
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  • Christoph A. Klein, Fraunhofer-Institut für Toxikologie und Experimentelle Medizin, University of Regensburg
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  • Bernhard Polzer, Fraunhofer-Institut für Toxikologie und Experimentelle Medizin
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  • Lubor Borsig, University of Zurich
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  • Mathias Heikenwalder, Technische Universitat Munchen, German Cancer Research Center, Heidelberg

Dynamic polarisation of tumour cells is essential for metastasis. While the role of polarisation during dedifferentiation and migration is well established, polarisation of metastasising tumour cells during phases of detachment has not been investigated. Here we identify and characterise a type of polarisation maintained by single cells in liquid phase termed single-cell (sc) polarity and investigate its role during metastasis. We demonstrate that sc polarity is an inherent feature of cells from different tumour entities that is observed in circulating tumour cells in patients. Functionally, we propose that the sc pole is directly involved in early attachment, thereby affecting adhesion, transmigration and metastasis. In vivo, the metastatic capacity of cell lines correlates with the extent of sc polarisation. By manipulating sc polarity regulators and by generic depolarisation, we show that sc polarity prior to migration affects transmigration and metastasis in vitro and in vivo.

Original languageEnglish
Article number887
JournalNature Communications
Volume9
Issue1
Number of pages20
ISSN2041-1723
DOIs
Publication statusPublished - 1 Dec 2018

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