UNASSIGNED: Voltage-gated @entity4024 channels (VGSCs) mediate action potential firing and regulate adhesion and migration in excitable cells. VGSCs are also expressed in @entity5 cells. In metastatic @entity0 ( @entity0 ) cells, the @entity1788 a subunit potentiates migration and invasion. In addition, the VGSC-inhibiting antiepileptic drug @entity3174 inhibits @entity5 growth and @entity3 . However, the functional activity of @entity1788 and its specific contribution to @entity5 progression in vivo has not been delineated. Here, we found that @entity1788 is up-regulated at the protein level in @entity0 compared with matched normal breast tissue. Na+ current, reversibly blocked by @entity1022 , was retained in @entity5 cells in @entity5 tissue slices, thus directly confirming functional VGSC activity in vivo. Stable down-regulation of @entity1788 expression significantly reduced @entity5 growth, local invasion into surrounding tissue, and @entity3 to liver, lungs and spleen in an orthotopic @entity0 model. @entity1788 down-regulation had no effect on cell proliferation or angiogenesis within the in @entity5 , but increased apoptosis. In vitro, @entity1788 down-regulation altered cell morphology and reduced @entity1759 expression, suggesting that VGSC activity may regulate cellular invasion via the @entity1759 -src-cortactin signaling axis. We conclude that @entity1788 is functionally active in @entity5 cells in @entity0 , enhancing growth and metastatic dissemination. These findings support the notion that compounds targeting @entity1788 may be useful for reducing @entity3 .

@entity1788 regulates XXXX growth and metastatic dissemination in vivo.

@entity1788 :: ('6331', 'Gene') :: ['Nav1.5'] @entity4024 :: ('D012964', 'Chemical') :: ['Na+'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer', 'breast tumors', 'BCa'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors', 'cancer'] @entity1022 :: ('MESH:D013779', 'Chemical') :: ['tetrodotoxin'] @entity1759 :: ('960', 'Gene') :: ['CD44'] @entity3174 :: ('MESH:D010672', 'Chemical') :: ['phenytoin'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis']
@entity0 :: (MESH:D001943,Disease) :: ['breast tumor']
