Title:Ion Transporters in Brain Tumors
Volume: 22
Issue: 10
Author(s): Damin Cong, Wen Zhu, John S. Kuo, Shaoshan Hu and Dandan Sun
Affiliation:
Keywords:
Bumetanide, cancer progression, cariporide, NKCC-1, NHE-1, targeted therapy.
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, sodiumpotassium-
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 (pHi) and extracellular pH (pHe) 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.
