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SHR Neuro Cancer Cardio Lipid Metab Microb

Leithner, K; Hirschmugl, B; Li, Y; Tang, B; Papp, R; Nagaraj, C; Stacher, E; Stiegler, P; Lindenmann, J; Olschewski, A; Olschewski, H; Hrzenjak, A.
TASK-1 Regulates Apoptosis and Proliferation in a Subset of Non-Small Cell Lung Cancers.
PLoS One. 2016; 11(6):e0157453-e0157453 Doi: 10.1371/journal.pone.0157453 [OPEN ACCESS]
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Leading authors Med Uni Graz
Hrzenjak Andelko
Leithner Katharina
Co-authors Med Uni Graz
Chandran Nagaraj
Hirschmugl Birgit
Li Yingji
Lindenmann Jörg
Olschewski Andrea
Olschewski Horst
Papp Rita
Stacher-Priehse Elvira
Stiegler Philipp
Tang Bi
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Abstract:
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.
Find related publications in this database (using NLM MeSH Indexing)
Apoptosis -
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Non-Small-Cell Lung - pathology
Cell Line, Tumor -
Cell Proliferation -
Gene Expression Regulation, Neoplastic -
Humans -
Lung - metabolism
Lung - pathology
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Potassium Channels, Tandem Pore Domain - genetics
Potassium Channels, Tandem Pore Domain - metabolism
RNA Interference -
RNA, Small Interfering - genetics

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