6324

SCN1B

sodium channel, voltage gated, type I beta subunit;SCN1B;sodium channel, voltage gated, type I beta subunit

sodium channel beta-1 subunit|sodium channel subunit beta-1|sodium channel, voltage-gated, type I, beta subunit

19q13.1

protein-coding

Voltage-gated Na(+) channels (VGSCs) are heteromeric proteins composed of pore-forming alpha subunits and smaller beta subunits. The beta subunits are multifunctional channel modulators and are members of the immunoglobulin superfamily of cell adhesion molecules (CAMs). beta1, encoded by SCN1B, is best characterized in the central nervous system (CNS), where it plays a critical role in regulating electrical excitability, neurite outgrowth and migration during development. beta1 is also expressed in breast cancer (BCa) cell lines, where it regulates adhesion and migration in vitro. In the present study, we found that SCN1B mRNA/beta1 protein were up-regulated in BCa specimens, compared with normal breast tissue. beta1 upregulation substantially increased tumour growth and metastasis in a xenograft model of BCa. beta1 over-expression also increased vascularization and reduced apoptosis in the primary tumours, and beta1 over-expressing tumour cells had an elongate morphology. In vitro, beta1 potentiated outgrowth of processes from BCa cells co-cultured with fibroblasts, via trans-homophilic adhesion. beta1-mediated process outgrowth in BCa cells required the presence and activity of fyn kinase, and Na(+) current, thus replicating the mechanism by which beta1 regulates neurite outgrowth in CNS neurons. We conclude that when present in breast tumours, beta1 enhances pathological growth and cellular dissemination. This study is the first demonstration of a functional role for beta1 in tumour growth and metastasis in vivo. We propose that beta1 warrants further study as a potential biomarker and targeting beta1-mediated adhesion interactions may have value as a novel anti-cancer therapy.