title: Glioma-specific cation conductance regulates migration and cell cycle progression.
abstract: In this study, we have investigated the role of a glioma-specific cation channel assembled from subunits of the Deg/epithelial sodium channel (ENaC) superfamily, in the regulation of migration and cell cycle progression in glioma cells. Channel inhibition by psalmotoxin-1 (PcTX-1) significantly inhibited migration and proliferation of D54-MG glioma cells. Both PcTX-1 and benzamil, an amiloride analog, caused cell cycle arrest of D54-MG cells in G(0)/G(1) phases (by 30 and 40%, respectively) and reduced cell accumulation in S and G(2)/M phases after 24 h of incubation. Both PcTX-1 and benzamil up-regulated expression of cyclin-dependent kinase inhibitor proteins p21(Cip1) and p27(Kip1). Similar results were obtained in U87MG and primary glioblastoma multiforme cells maintained in primary culture and following knockdown of one of the component subunits, ASIC1. In contrast, knocking down δENaC, which is not a component of the glioma cation channel complex, had no effect on cyclin-dependent kinase inhibitor expression. Phosphorylation of ERK1/2 was also inhibited by PcTX-1, benzamil, and knockdown of ASIC1 but not δENaC in D54MG cells. Our data suggest that a specific cation conductance composed of acid-sensing ion channels and ENaC subunits regulates migration and cell cycle progression in gliomas.
authors: Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors: Arun K
authors: AK
authors: Rooj
authors: Carmel M
authors: CM
authors: McNicholas
authors: Rafal
authors: R
authors: Bartoszewski
authors: Zsuzsanna
authors: Z
authors: Bebok
authors: Dale J
authors: DJ
authors: Benos
authors: Catherine M
authors: CM
authors: Fuller
mesh_terms: D062565:Acid Sensing Ion Channels; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010455:Peptides; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology
chemical_list: C568266:ASIC1 protein, human; D062565:Acid Sensing Ion Channels; C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C413209:PcTX1 protein, Psalmopoeus cambridgei; D010455:Peptides; C507051:SCNN1D protein, human; D015222:Sodium Channels; D013111:Spider Venoms; C013407:benzamil; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000584:Amiloride