Nature Communications · 2018 · 61 citations · 40 references
MedicineCancer BiologyCell BiologyCell AdhesionCell PolarityMetastasisCell Adhesion In MetastasisCell MigrationCirculating Tumor CellsMetastatic DisseminationAdhesion-dependent MigrationCell Polarity In MigrationCell Polarization MechanismsCirculating Tumor Cell MigrationEarly AttachmentMetastatic Cell DetachmentPolarity-driven Cell MigrationPolarized Cell Migration
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.
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