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

Nature communications (2016-12-06)
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, Sébastien Roger
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
Anti-SCN4B antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution