PUBLICATION
SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer
- Authors
- Bon, E., Driffort, V., Gradek, F., Martinez-Caceres, C., Anchelin, M., Pelegrin, P., Cayuela, M.L., Marionneau-Lambot, S., Oullier, T., Guibon, R., Fromont, G., Gutierrez-Pajares, J.L., Domingo, I., Piver, E., Moreau, A., Burlaud-Gaillard, J., Frank, P.G., Chevalier, S., Besson, P., Roger, S.
- ID
- ZDB-PUB-180905-7
- Date
- 2016
- Source
- Nature communications 7: 13648 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Breast Neoplasms/genetics*
- Breast Neoplasms/pathology*
- Breast Neoplasms/ultrastructure
- Cell Line, Tumor
- Cell Movement*/genetics
- Cell Proliferation
- Disease Progression
- Down-Regulation/genetics
- Epithelial Cells/metabolism
- Extracellular Matrix/metabolism
- Female
- Gene Expression Regulation, Neoplastic
- Genes, Tumor Suppressor*
- Human Umbilical Vein Endothelial Cells/metabolism
- Humans
- Ion Channel Gating
- Mice, Nude
- Neoplasm Invasiveness
- Neoplasm Metastasis
- Prognosis
- Protein Subunits/metabolism
- Sodium Channels/metabolism
- Voltage-Gated Sodium Channel beta-4 Subunit/genetics*
- Voltage-Gated Sodium Channel beta-4 Subunit/metabolism
- Zebrafish
- rhoA GTP-Binding Protein/metabolism
- PubMed
- 27917859 Full text @ Nat. Commun.
Citation
Bon, E., Driffort, V., Gradek, F., Martinez-Caceres, C., Anchelin, M., Pelegrin, P., Cayuela, M.L., Marionneau-Lambot, S., Oullier, T., Guibon, R., Fromont, G., Gutierrez-Pajares, J.L., Domingo, I., Piver, E., Moreau, A., Burlaud-Gaillard, J., Frank, P.G., Chevalier, S., Besson, P., Roger, S. (2016) SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer. Nature communications. 7:13648.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping