title: Ion transporters in brain tumors.
abstract: Ion transporters are important in regulation of ionic homeostasis, cell volume, and cellular signal transduction under physiological conditions. They have recently emerged as important players in cancer progression. In this review, we discussed two important ion transporter proteins, sodium-potassium-chloride cotransporter isoform 1 (NKCC-1) and sodium-hydrogen exchanger isoform 1 (NHE-1) in Glioblastoma multiforme (GBM) and other malignant tumors. NKCC-1 is a Na(+)- dependent Cl(-) transporter that mediates the movement of Na(+), K(+), and Cl(-) ions across the plasma membrane and maintains cell volume and intracellular K(+) and Cl(-) homeostasis. NHE-1 is a ubiquitously expressed cell membrane protein which regulates intracellular pH (pH(i)) and extracellular pH (pH(e)) homeostasis and cell volume. Here, we summarized recent pre-clinical experimental studies on NKCC-1 and NHE-1 in GBM and other malignant tumors, such as breast cancer, hepatocellular carcinoma, and lung cancer cells. These studies illustrated that pharmacological inhibition or down-regulation of these ion transporter proteins reduces proliferation, increases apoptosis, and suppresses migration and invasion of cancer cells. These new findings reveal the potentials of these ion transporters as new targets for cancer diagnosis and/or treatment.
authors.forename: Damin
authors.initials: D
authors.lastname: Cong
authors.forename: Wen
authors.initials: W
authors.lastname: Zhu
authors.forename: John S
authors.initials: JS
authors.lastname: Kuo
authors.forename: Shaoshan
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Neurology, University of Pittsburgh Medical School, S-598 South Biomedical Science Tower (BST), 3500 Terrace St., Pittsburgh, PA 15213, USA. sund@upmc.edu.
authors.forename: Dandan
authors.initials: D
authors.lastname: Sun
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; C578877:SLC12A2 protein, human; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D064506:Solute Carrier Family 12, Member 2