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© 2022, Fanfone et al. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Confined migration promotes cancer metastasis through resistance to anoikis and increased invasiveness
Author
Fanfone Deborah; Wu Zhichong; Mammi Jade; Berthenet Kevin; Neves, David; Weber, Kathrin; Halaburkova Andrea; Virard François; Bunel Félix; Jamard Catherine; Hernandez-Vargas, Hector; Tait Stephen WG; Hennino Ana; Ichim Gabriel
University/institution
U.S. National Institutes of Health/National Library of Medicine
Publication year
2022
Publication date
2022
Publisher
eLife Sciences Publications Ltd.
e-ISSN
2050084X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2645789919
Copyright
© 2022, Fanfone et al. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.