Confined migration promotes cancer metastasis through resistance to anoikis and increased invasiveness

Fanfone, D. et al. (2022) Confined migration promotes cancer metastasis through resistance to anoikis and increased invasiveness. eLife, 11, e73150. (doi: 10.7554/eLife.73150) (PMID:35256052) (PMCID:PMC8903834)

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Mechanical stress is known to fuel several hallmarks of cancer, ranging from genome instability to uncontrolled proliferation or invasion. Cancer cells are constantly challenged by mechanical stresses not only in the primary tumour but also during metastasis. However, this latter has seldom been studied with regards to mechanobiology, in particular resistance to anoikis, a cell death programme triggered by loss of cell adhesion. Here, we show in vitro that migrating breast cancer cells develop resistance to anoikis following their passage through microporous membranes mimicking confined migration (CM), a mechanical constriction that cancer cells encounter during metastasis. This CM-induced resistance was mediated by Inhibitory of Apoptosis Proteins, and sensitivity to anoikis could be restored after their inhibition using second mitochondria-derived activator of caspase (SMAC) mimetics. Anoikis-resistant mechanically stressed cancer cells displayed enhanced cell motility and evasion from natural killer cell-mediated immune surveillance, as well as a marked advantage to form lung metastatic lesions in mice. Our findings reveal that CM increases the metastatic potential of breast cancer cells.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Tait, Professor Stephen
Creator Roles:
Tait, S. W.G.Resources
Authors: Fanfone, D., Wu, Z., Mammi, J., Berthenet, K., Neves, D., Weber, K., Halaburkova, A., Virard, F., Bunel, F., Jamard, C., Hernandez-Vargas, H., Tait, S. W.G., Hennino, A., and Ichim, G.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2022 Fanfone et al.
First Published:First published in eLife 11: e73150
Publisher Policy:Reproduced under a Creative Commons License

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