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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]
Web of Science
PubMed
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- Leading authors Med Uni Graz
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Hrzenjak Andelko
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Leithner Katharina
- Co-authors Med Uni Graz
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Chandran Nagaraj
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Hirschmugl Birgit
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Li Yingji
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Lindenmann Jörg
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Olschewski Andrea
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Olschewski Horst
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Papp Rita
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Stacher-Priehse Elvira
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Stiegler Philipp
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Tang Bi
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- Abstract:
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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.
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Carcinoma, Non-Small-Cell Lung - genetics
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Carcinoma, Non-Small-Cell Lung - metabolism
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