Publication: SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer
Authors
Bon, Emeline ; Driffort, Virginie ; Gradek, Frédéric ; Anchelin, Monique ; Cayuela, María Luisa ; Marionneau Lambot, Séverine ; Oullier, Thibauld ; Guibon, Roseline ; Fromont, Gaëlle ; Gutierrez Pajares, Jorge L. ; Domingo, Isabelle ; Piver, Eric ; Moreau, Alain ; Burlaud Gaillard, Julien ; Frank, Philippe G. ; Chevalier, Stésphan ; Besson, Pierre ; Roger, Sébastien ; Martínez Cáceres, Carlos Manuel ; Pelegrín Vivancos, Pablo
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Publisher
Nature Research
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DOI
https://doi.org/10.1038/ncomms13648
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info:eu-repo/semantics/article
Description
© The Author(s) 2016. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/
This document is the Published version of a Published Work that appeared in final form in Nature Communications. To access the final edited and published work see https://doi.org/10.1038/ncomms13648
Abstract
The development of metastases largely relies on the capacity of cancer cells to invade extracellular matrices (ECM) using two invasion modes termed ‘mesenchymal’ and ‘amoeboid’, with possible transitions between these modes. Here we show that the SCN4B gene, encoding for the β4 protein, initially characterized as an auxiliary subunit of voltage-gated sodium channels (NaV) in excitable tissues, is expressed in normal epithelial cells and that reduced β4 protein levels in breast cancer biopsies correlate with high-grade primary and metastatic tumours. In cancer cells, reducing β4 expression increases RhoA activity, potentiates cell migration and invasiveness, primary tumour growth and metastatic spreading, by promoting the acquisition of an amoeboid–mesenchymal hybrid phenotype. This hyperactivated migration is independent of NaV and is prevented by overexpression of the intracellular C-terminus of β4. Conversely, SCN4B overexpression reduces cancer cell invasiveness and tumour progression, indicating that SCN4B/β4 represents a metastasis-suppressor gene.
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Citation
Nature Communications, 2016, Vol. 7 : 13648
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by/4.0/