Nuclear rupture induced by capillary constriction forces promotes differential effects on metastatic and normal breast cells.

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ICR Authors

Bakal, Christopher

Authors

Perea Paizal, J
Au, SH
Bakal, C

Document Type

Journal Article

Date

2024-06-26

Date Accepted

2024-06-12

Abstract

During metastatic dissemination, circulating tumour cells (CTCs) enter capillary beds, where they experience mechanical constriction forces. The transient and persistent effects of these forces on CTCs behaviour remain poorly understood. Here, we developed a high-throughput microfluidic platform mimicking human capillaries to investigate the impact of mechanical constriction forces on malignant and normal breast cell lines. We observed that capillary constrictions induced nuclear envelope rupture in both cancer and normal cells, leading to transient changes in nuclear and cytoplasmic area. Constriction forces transiently activated cGAS/STING and pathways involved in inflammation (NF-κB, STAT and IRF3), especially in the non-malignant cell line. Furthermore, the non-malignant cell line experienced transcriptional changes, particularly downregulation of epithelial markers, while the metastatic cell lines showed minimal alterations. These findings suggest that mechanical constriction forces within capillaries may promote differential effects in malignant and normal cell lines.

Citation

Scientific Reports, 2024, 14 (1), pp. 14793 -

DOI

10.1038/s41598-024-64733-x
10.1038/s41598-024-64733-x

URI

https://repository.icr.ac.uk/handle/internal/6342

Rights

http://creativecommons.org/licenses/by/4.0/

Source Title

Scientific Reports

Publisher

NATURE PORTFOLIO

ISSN

2045-2322

eISSN

2045-2322
2045-2322

Collections

Cancer Biology

Research Team

Dynamical Cell Systems

Notes