A novel adhesion molecule in human breast cancer cells: Voltage-gated Na+ channel beta 1 subunit

TY - JOUR

T1 - A novel adhesion molecule in human breast cancer cells: Voltage-gated Na+ channel beta 1 subunit

AU - Chioni, Athina-Myrto

AU - Brackenbury, William J.

AU - Calhoun, Jeffrey D.

AU - Isom, Lori L.

AU - Djamgoz, Mustafa B. A.

PY - 2009/5

Y1 - 2009/5

N2 - Voltage-gated Na+ channels (VGSCs), predominantly the 'neonatal' splice form of Na(v)1.5 (nNa(v)1.5), are upregulated in metastatic breast cancer (BCa) and potentiate metastatic cell behaviours. VGSCs comprise one pore-forming alpha subunit and one or more beta subunits. The latter modulate VGSC expression and gating, and can function as cell adhesion molecules of the immunoglobulin superfamily. The aims of this study were (1) to determine which beta subunits were expressed in weakly metastatic MCF-7 and strongly metastatic MDA-MB-231 human BCa cells, and (2) to investigate the possible role of beta subunits in adhesion and migration. In both cell lines, the beta subunit mRNA expression profile was SCN1B (encoding beta 1)>> SCN4B (encoding beta 4) > SCN2B (encoding beta 2); SCN3B (encoding beta 3) was not detected. MCF-7 cells had much higher levels of all beta subunit mRNAs than MDA-MB-231 cells, and beta 1 mRNA was the most abundant. Similarly, beta 1 protein was strongly expressed in MCF-7 and barely detectable in MDA-MB-231 cells. In MCF-7 cells transfected with siRNA targeting beta 1, adhesion was reduced by 35%, while migration was increased by 121%. The increase in migration was reversed by tetrodotoxin (TFX). In addition, levels of nNa(v)1.5 mRNA and protein were increased following beta 1 down-regulation. Stable expression of beta 1 in MDA-MB-231 cells increased functional VGSC activity, process length and adhesion, and reduced lateral motility and proliferation. We conclude that beta 1 is a novel cell adhesion molecule in BCa cells and can control VGSC (nNa(v)1.5) expression and, concomitantly, cellular migration. (C) 2008 Elsevier Ltd. All rights reserved.

AB - Voltage-gated Na+ channels (VGSCs), predominantly the 'neonatal' splice form of Na(v)1.5 (nNa(v)1.5), are upregulated in metastatic breast cancer (BCa) and potentiate metastatic cell behaviours. VGSCs comprise one pore-forming alpha subunit and one or more beta subunits. The latter modulate VGSC expression and gating, and can function as cell adhesion molecules of the immunoglobulin superfamily. The aims of this study were (1) to determine which beta subunits were expressed in weakly metastatic MCF-7 and strongly metastatic MDA-MB-231 human BCa cells, and (2) to investigate the possible role of beta subunits in adhesion and migration. In both cell lines, the beta subunit mRNA expression profile was SCN1B (encoding beta 1)>> SCN4B (encoding beta 4) > SCN2B (encoding beta 2); SCN3B (encoding beta 3) was not detected. MCF-7 cells had much higher levels of all beta subunit mRNAs than MDA-MB-231 cells, and beta 1 mRNA was the most abundant. Similarly, beta 1 protein was strongly expressed in MCF-7 and barely detectable in MDA-MB-231 cells. In MCF-7 cells transfected with siRNA targeting beta 1, adhesion was reduced by 35%, while migration was increased by 121%. The increase in migration was reversed by tetrodotoxin (TFX). In addition, levels of nNa(v)1.5 mRNA and protein were increased following beta 1 down-regulation. Stable expression of beta 1 in MDA-MB-231 cells increased functional VGSC activity, process length and adhesion, and reduced lateral motility and proliferation. We conclude that beta 1 is a novel cell adhesion molecule in BCa cells and can control VGSC (nNa(v)1.5) expression and, concomitantly, cellular migration. (C) 2008 Elsevier Ltd. All rights reserved.

KW - Adhesion

KW - Breast cancer

KW - Metastasis

KW - Migration

KW - Voltage-gated Na+ channel

KW - RAT PROSTATE-CANCER

KW - SODIUM-CHANNEL

KW - IN-VITRO

KW - FUNCTIONAL EXPRESSION

KW - SKELETAL-MUSCLE

KW - LUNG-CANCER

KW - NEURITE OUTGROWTH

KW - AUXILIARY SUBUNIT

KW - CARDIAC MYOCYTES

KW - BETA(1) SUBUNIT

UR - http://www.scopus.com/inward/record.url?scp=59649120237&partnerID=8YFLogxK

U2 - 10.1016/j.biocel.2008.11.001

DO - 10.1016/j.biocel.2008.11.001

M3 - Article

SN - 1357-2725

VL - 41

SP - 1216

EP - 1227

JO - International Journal of Biochemistry and Cell Biology

JF - International Journal of Biochemistry and Cell Biology

IS - 5

ER -