Glioma-specific cation conductance regulates migration and cell cycle progression.

Academic Article

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 ╬┤ENaC, 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 ╬┤ENaC 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.
  • Published In

    Keywords

  • Acid Sensing Ion Channels, Amiloride, Cell Cycle Checkpoints, Cell Line, Tumor, Cell Movement, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Epithelial Sodium Channel Blockers, Epithelial Sodium Channels, G1 Phase, Glioma, Humans, Neoplasm Proteins, Nerve Tissue Proteins, Peptides, Resting Phase, Cell Cycle, Sodium Channels, Spider Venoms
  • Digital Object Identifier (doi)

    Author List

  • Rooj AK; McNicholas CM; Bartoszewski R; Bebok Z; Benos DJ; Fuller CM
  • Start Page

  • 4053
  • End Page

  • 4065
  • Volume

  • 287
  • Issue

  • 6