机译
通过微循环挤压:循环肿瘤细胞对种子转移的生存适应
摘要:When a CTC encounters a capillary bed, two situations can take place: it can get arrested and initiates extravasation, or the CTC can transit through the capillary and escape from it, enabling its migration to a more distant capillary bed. During transit and/or arrest, CTCs undergo intense cell deformation, which can induce changes in the mechanotransduction of signalling pathways, such as RhoA–ROCK and YAP/TAZ,7,25,47–49 resulting in an increase of cell invasiveness and survival (see inset “Signalling changes”). Upon activation, YAP/TAZ gets translocated to the nucleus, inducing changes in the transcription activity. The stretching of the cellular membrane favoured by the intense deformation activates mechanosensors that may contribute to cancer progression.8 Constriction forces in capillaries also provoke nuclear deformation (see inset “Nuclear changes”), leading to chromatin rearrangement and gene regulation towards epithelial-to-mesenchymal transition (EMT).9,10,75 Nuclear deformation can result in the production of nuclear blebs after nuclear lamin rupture, inducing an exchange of nucleo-cytoplasmatic contents and thus, mislocalisation of nuclear repair factors.10,18 Consequently, the repair of the nuclear envelope (NE) may be delayed, resulting in an increase in DNA damage. This nuclear damage is one of the possible sources of chromosomal instability (CIN), which has proven to drive metastasis.80 Shear forces experienced by CTCs transiting and/or arrested in capillaries can produce cytoplasm blebs, which upon attachment to the capillary wall, attract immune-interacting intermediates that promote extravasation42 (see inset “Recruitment of immune populations”). In the event that CTCs manage to squeeze through the capillary preventing arrest, morphological changes are observed in the nucleus and the cytoplasm as a result of severe cell deformation.9 Overall, capillary constriction forces may induce long-term effects on cell fate that may contribute to the metastatic potency.