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.

Chair of Experimental Medicine and Therapy Research University of Regensburg 93053 Regensburg Germany

Department of Dermatology University Hospital Regensburg 93042 Regensburg Germany

Department of Dermatology Venereology and Allergology University Medical Center Mannheim Ruprecht Karl University of Heidelberg 68167 Mannheim Germany

Department of Internal Medicine 2 Klinikum rechts der Isar Technische Universität München 81675 Munich Germany

Department of Molecular Biology and Genetics Aarhus University 8000 Aarhus Denmark

Department of Surgery Klinikum rechts der Isar Technische Universität München 81675 Munich Germany

Department of Surgical Pathology University Hospital Zurich 8091 Zurich Switzerland

Department of Systems Toxicology Leibnitz Research Cenrtre for Working Environment and Human Factors 44139 Dortmund Germany

Division of Stem Cells and Cancer Deutsches Krebsforschungszentrum 69120 Heidelberg Germany

Divison of Chronic Inflammation and Cancer German Cancer Research Center 69120 Heidelberg Germany

Electron Microscopy Core Facility European Molecular Biology Laboratory 69117 Heidelberg Germany

Frauenklinik University Medical Centre Mannheim 68167 Mannheim Germany

German Cancer Consortium 69120 Heidelberg Germany

Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH 69120 Heidelberg Germany

Institut für Klinische Chemie und Pathobiochemie Klinikum rechts der Isar Technische Universität München 81675 Munich Germany

Institut für Medizinische Statistik und Epidemiologie Klinikum rechts der Isar Technische Universität München 81675 Munich Germany

Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic 14220 Prague Czech Republic

Institute of Physiology Zurich Center for Integrative Human Physiology University of Zurich 8057 Zurich Switzerland

Institute of Virology Technische Universität München Helmholtz Center Munich 81675 Munich Germany

Project Group Personalized Tumour Therapy Fraunhofer Institut für Toxikologie und Experimentelle Medizin 93053 Regensburg Germany

Skin Cancer Unit Deutsches Krebsforschungszentrum 69120 Heidelberg Germany

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