| First Author | Bon E | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 13648 | PubMed ID | 27917859 |
| Mgi Jnum | J:243164 | Mgi Id | MGI:5907794 |
| Doi | 10.1038/ncomms13648 | Citation | Bon E, et al. (2016) SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer. Nat Commun 7:13648 |
| abstractText | 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 beta4 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 beta4 protein levels in breast cancer biopsies correlate with high-grade primary and metastatic tumours. In cancer cells, reducing beta4 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 beta4. Conversely, SCN4B overexpression reduces cancer cell invasiveness and tumour progression, indicating that SCN4B/beta4 represents a metastasis-suppressor gene. |
