SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27917859.
- Also identified by DOI 10.1038/ncomms13648 and PMC identifier 5150224.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (Na<sub>V</sub>) 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 Na<sub>V</sub> 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.
Medical subject headings
- Breast Neoplasms
- Cell Movement
- Genes, Tumor Suppressor
- Voltage-Gated Sodium Channel beta-4 Subunit