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 l...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4905626?pdf=render |
| _version_ | 1828340773235458048 |
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| author | Katharina Leithner Birgit Hirschmugl Yingji Li Bi Tang Rita Papp Chandran Nagaraj Elvira Stacher Philipp Stiegler Jörg Lindenmann Andrea Olschewski Horst Olschewski Andelko Hrzenjak |
| author_facet | Katharina Leithner Birgit Hirschmugl Yingji Li Bi Tang Rita Papp Chandran Nagaraj Elvira Stacher Philipp Stiegler Jörg Lindenmann Andrea Olschewski Horst Olschewski Andelko Hrzenjak |
| author_sort | Katharina Leithner |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T23:02:26Z |
| format | Article |
| id | doaj.art-f29e5ea005f748e4b4e24e4b9bbafaa7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T23:02:26Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f29e5ea005f748e4b4e24e4b9bbafaa72022-12-22T02:25:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01116e015745310.1371/journal.pone.0157453TASK-1 Regulates Apoptosis and Proliferation in a Subset of Non-Small Cell Lung Cancers.Katharina LeithnerBirgit HirschmuglYingji LiBi TangRita PappChandran NagarajElvira StacherPhilipp StieglerJörg LindenmannAndrea OlschewskiHorst OlschewskiAndelko HrzenjakLung 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.http://europepmc.org/articles/PMC4905626?pdf=render |
| spellingShingle | Katharina Leithner Birgit Hirschmugl Yingji Li Bi Tang Rita Papp Chandran Nagaraj Elvira Stacher Philipp Stiegler Jörg Lindenmann Andrea Olschewski Horst Olschewski Andelko Hrzenjak TASK-1 Regulates Apoptosis and Proliferation in a Subset of Non-Small Cell Lung Cancers. PLoS ONE |
| title | TASK-1 Regulates Apoptosis and Proliferation in a Subset of Non-Small Cell Lung Cancers. |
| title_full | TASK-1 Regulates Apoptosis and Proliferation in a Subset of Non-Small Cell Lung Cancers. |
| title_fullStr | TASK-1 Regulates Apoptosis and Proliferation in a Subset of Non-Small Cell Lung Cancers. |
| title_full_unstemmed | TASK-1 Regulates Apoptosis and Proliferation in a Subset of Non-Small Cell Lung Cancers. |
| title_short | TASK-1 Regulates Apoptosis and Proliferation in a Subset of Non-Small Cell Lung Cancers. |
| title_sort | task 1 regulates apoptosis and proliferation in a subset of non small cell lung cancers |
| url | http://europepmc.org/articles/PMC4905626?pdf=render |
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