TASK-1 Regulates Apoptosis and Proliferation in a Subset of Non-Small Cell Lung Cancers

• Published in: PloS one 2016-06, Vol.11 (6), p.e0157453-e0157453
• Main Authors: Leithner, Katharina, Hirschmugl, Birgit, Li, Yingji, Tang, Bi, Papp, Rita, Nagaraj, Chandran, Stacher, Elvira, Stiegler, Philipp, Lindenmann, Jörg, Olschewski, Andrea, Olschewski, Horst, Hrzenjak, Andelko
• Format: Article
• Language: English
• Subjects: Adenosine triphosphatase; Anesthesiology; Antibiotics; Apoptosis; Biology and life sciences; Biotin; Boltzmann, Ludwig Eduard (1844-1906); Cancer; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Care and treatment; Cell growth; Cell Line, Tumor; Cell Proliferation; Channels; Depolarization; Development and progression; Efflux; Gene Expression Regulation, Neoplastic; Genetic aspects; Genetic regulation; Glutamine; Health aspects; Humans; Hypoxia; Inositol; Internal medicine; Lung - metabolism; Lung - pathology; Lung cancer; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical research; Medicine; Medicine and Health Sciences; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Non-small cell lung cancer; Non-small cell lung carcinoma; Nutrient transport; Nutrients; pH effects; Physical Sciences; Potassium; Potassium channels; Potassium Channels, Tandem Pore Domain - genetics; Potassium Channels, Tandem Pore Domain - metabolism; Pulmonary arteries; RNA Interference; RNA, Small Interfering - genetics; siRNA; Smooth muscle; Surgery; Transport; Tumor cell lines; Vitamins
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0157453

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.