Open AccessTASK-1 Regulates Apoptosis and Proliferation in a Subset of Non-Small Cell Lung Cancers
Author(s) -
Katharina Leithner,
Birgit Hirschmugl,
Yingji Li,
Bi Tang,
Rita Papp,
Chandran Nagaraj,
Elvira Stacher,
Philipp Stiegler,
Jörg Lindenmann,
Andrea Olschewski,
Horst Olschewski,
Andelko Hrzenjak
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0157453
Subject(s) - apoptosis , lung cancer , a549 cell , cell growth , biology , cancer research , gene knockdown , cell culture , microbiology and biotechnology , chemistry , medicine , biochemistry , genetics
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.