TASK-1 Regulates Apoptosis and Proliferation in a Subset of Non-Small Cell Lung Cancers.
Lung cancer is the leading cause of cancer deaths worldwide; survival times are poor despite therapy. The role of the two-pore domain K+ (K2P) channel TASK-1 (KCNK3) in lung cancer is at present unknown. We found that TASK-1 is expressed in non-small cell lung cancer (NSCLC) cell lines at variable levels. In a highly TASK-1 expressing NSCLC cell line, A549, a characteristic pH- and hypoxia-sensitive non-inactivating K+ current was measured, indicating the presence of functional TASK-1 channels. Inhibition of TASK-1 led to significant depolarization in these cells. Knockdown of TASK-1 by siRNA significantly enhanced apoptosis and reduced proliferation in A549 cells, but not in weakly TASK-1 expressing NCI-H358 cells. Na+-coupled nutrient transport across the cell membrane is functionally coupled to the efflux of K+ via K+ channels, thus TASK-1 may potentially influence Na+-coupled nutrient transport. In contrast to TASK-1, which was not differentially expressed in lung cancer vs. normal lung tissue, we found the Na+-coupled nutrient transporters, SLC5A3, SLC5A6, and SLC38A1, transporters for myo-inositol, biotin and glutamine, respectively, to be significantly overexpressed in lung adenocarcinomas. In summary, we show for the first time that the TASK-1 channel regulates apoptosis and proliferation in a subset of NSCLC.
Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Katharina
K
Leithner
Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.
Birgit
B
Hirschmugl
Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Yingji
Y
Li
Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Bi
B
Tang
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Rita
R
Papp
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.|Experimental Anesthesiology, University Clinic for Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.
Chandran
C
Nagaraj
Institute of Pathology, Medical University of Graz, Graz, Austria.
Elvira
E
Stacher
Division of Transplant Surgery, Department of Surgery, Medical University of Graz, Graz, Austria.
Philipp
P
Stiegler
Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Medical University of Graz, Graz, Austria.
Jörg
J
Lindenmann
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.|Institute of Physiology, Medical University of Graz, Graz, Austria.
Andrea
A
Olschewski
Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Horst
H
Olschewski
Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.|Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Andelko
A
Hrzenjak
D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D034741:RNA, Small Interfering; C420132:potassium channel subfamily K member 3