SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer

Emeline Bon, Virginie Driffort, Frédéric Gradek, Carlos Martinez-Caceres, Monique Anchelin, Pablo Pelegrin, Maria-Luisa Cayuela, Séverine Marionneau-Lambot, Thibauld Oullier, Roseline Guibon, Gaëlle Fromont, Jorge L. Gutierrez-Pajares, Isabelle Domingo, Eric Piver, Alain Moreau, Julien Burlaud-Gaillard, Philippe G. Frank, Stéphan Chevalier, Pierre Besson and Sébastien Roger ()
Additional contact information
Emeline Bon: Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours
Virginie Driffort: Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours
Frédéric Gradek: Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours
Carlos Martinez-Caceres: Inflammation and Experimental Surgery Unit, CIBERehd, Murcia’s BioHealth Research Institute IMIB-Arrixaca, Clinical University Hospital Virgen de la Arrixaca
Monique Anchelin: Telomerase, Cancer and Aging Group, Hospital Virgen de la Arrixaca
Pablo Pelegrin: Inflammation and Experimental Surgery Unit, CIBERehd, Murcia’s BioHealth Research Institute IMIB-Arrixaca, Clinical University Hospital Virgen de la Arrixaca
Maria-Luisa Cayuela: Telomerase, Cancer and Aging Group, Hospital Virgen de la Arrixaca
Séverine Marionneau-Lambot: Cancéropôle du Grand Ouest, Plateforme In Vivo
Thibauld Oullier: Cancéropôle du Grand Ouest, Plateforme In Vivo
Roseline Guibon: Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours
Gaëlle Fromont: Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours
Jorge L. Gutierrez-Pajares: Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours
Isabelle Domingo: Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours
Eric Piver: CHRU de Tours, 2 Boulevard Tonnellé
Alain Moreau: Inserm, U966, Université François-Rabelais de Tours
Julien Burlaud-Gaillard: Laboratoire de Biologie Cellulaire-Microscopie Electronique, Faculté de Médecine, Université François-Rabelais de Tours
Philippe G. Frank: Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours
Stéphan Chevalier: Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours
Pierre Besson: Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours
Sébastien Roger: Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours

Nature Communications, 2016, vol. 7, issue 1, 1-18

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13648

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