Suppression of ClC-3 channel expression reduces migration of nasopharyngeal carcinoma cells.
Recent studies suggest that chloride (Cl-) channels regulate tumor cell migration. In this report, we have used antisense oligonucleotides specific for ClC-3, the most likely molecular candidate for the volume-activated Cl- channel, to investigate the role of ClC-3 in the migration of nasopharyngeal carcinoma cells (CNE-2Z) in vitro. We found that suppression of ClC-3 expression inhibited the migration of CNE-2Z cells in a concentration-dependent manner. Whole-cell patch-clamp recordings and image analysis further demonstrated that ClC-3 suppression inhibited the volume-activated Cl- current (I(Cl,vol)) and regulatory volume decrease (RVD) of CNE-2Z cells. The expression of ClC-3 positively correlated with cell migration, I(Cl,vol) and RVD. These results strongly suggest that ClC-3 is a component or regulator of the volume-activated Cl- channel. ClC-3 may regulate CNE-2Z cell migration by modulating cell volume. ClC-3 may be a new target for cancer therapies.
Mao
Jianwen
J
Institute of Basic Medical Sciences and Department of Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Chen
Lixin
L
Xu
Bin
B
Wang
Lijing
L
Li
Hongzhi
H
Guo
Jiao
J
Li
Weidong
W
Nie
Sihuai
S
Jacob
Tim J C
TJ
Wang
Liwei
L
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D002712:Chlorides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D014162:Transfection
D018118:Chloride Channels; D002712:Chlorides; C115376:ClC-3 channel; D016376:Oligonucleotides, Antisense