Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2003 Jun 24;10013:7803-7. doi: 10.1073/pnas.1232448100.
Show Gene links
Show Anatomy links
Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function.
Pei L
,
Wiser O
,
Slavin A
,
Mu D
,
Powers S
,
Jan LY
,
Hoey T
.
???displayArticle.abstract??? TASK3 gene (Kcnk9) is amplified and overexpressed in several types of human carcinomas. In this report, we demonstrate that a point mutation (G95E) within the consensus K+ filter of TASK3 not only abolished TASK3 potassium channel activity but also abrogated its oncogenic functions, including proliferation in low serum, resistance to apoptosis, and promotion of tumor growth. Furthermore, we provide evidence that TASK3G95E is a dominant-negative mutation, because coexpression of the wild-type and the mutant TASK3 resulted in inhibition of K+ current of wild-type TASK3 and its tumorigenicity in nude mice. These results establish a direct link between the potassium channel activity of TASK3 and its oncogenic functions and imply that blockers for this potassium channel may have therapeutic potential for the treatment of cancers.
Amigorena,
Ion channels and B cell mitogenesis.
1990, Pubmed
Amigorena,
Ion channels and B cell mitogenesis.
1990,
Pubmed
Bianchi,
herg encodes a K+ current highly conserved in tumors of different histogenesis: a selective advantage for cancer cells?
1998,
Pubmed
,
Xenbase
Buckler,
An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells.
2000,
Pubmed
Chapman,
Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel.
2000,
Pubmed
,
Xenbase
Czirják,
Formation of functional heterodimers between the TASK-1 and TASK-3 two-pore domain potassium channel subunits.
2002,
Pubmed
,
Xenbase
Czirják,
TASK (TWIK-related acid-sensitive K+ channel) is expressed in glomerulosa cells of rat adrenal cortex and inhibited by angiotensin II.
2000,
Pubmed
,
Xenbase
Duprat,
TASK, a human background K+ channel to sense external pH variations near physiological pH.
1997,
Pubmed
,
Xenbase
Goldstein,
Potassium leak channels and the KCNK family of two-P-domain subunits.
2001,
Pubmed
Hartness,
Combined antisense and pharmacological approaches implicate hTASK as an airway O(2) sensing K(+) channel.
2001,
Pubmed
Heginbotham,
Mutations in the K+ channel signature sequence.
1994,
Pubmed
,
Xenbase
Jensen,
Inhibition of T cell proliferation by selective block of Ca(2+)-activated K(+) channels.
1999,
Pubmed
Karschin,
Expression pattern in brain of TASK-1, TASK-3, and a tandem pore domain K(+) channel subunit, TASK-5, associated with the central auditory nervous system.
2001,
Pubmed
,
Xenbase
Kim,
TASK-3, a new member of the tandem pore K(+) channel family.
2000,
Pubmed
Lepple-Wienhues,
K+ channels and the intracellular calcium signal in human melanoma cell proliferation.
1996,
Pubmed
Lesage,
Molecular and functional properties of two-pore-domain potassium channels.
2000,
Pubmed
Lin,
Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation.
1993,
Pubmed
Lopes,
Block of Kcnk3 by protons. Evidence that 2-P-domain potassium channel subunits function as homodimers.
2001,
Pubmed
,
Xenbase
Meadows,
Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel.
2001,
Pubmed
,
Xenbase
Mu,
Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene.
2003,
Pubmed
Nilius,
Potassium channels and regulation of proliferation of human melanoma cells.
1992,
Pubmed
Pancrazio,
Voltage-activated K+ conductance and cell proliferation in small-cell lung cancer.
1993,
Pubmed
Pardo,
Oncogenic potential of EAG K(+) channels.
1999,
Pubmed
Patel,
Inhalational anesthetics activate two-pore-domain background K+ channels.
1999,
Pubmed
Pei,
PRC17, a novel oncogene encoding a Rab GTPase-activating protein, is amplified in prostate cancer.
2002,
Pubmed
Rader,
T cell activation is regulated by voltage-dependent and calcium-activated potassium channels.
1996,
Pubmed
Rajan,
TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histiding as pH sensor.
2000,
Pubmed
,
Xenbase
Rouzaire-Dubois,
K+ channel block-induced mammalian neuroblastoma cell swelling: a possible mechanism to influence proliferation.
1998,
Pubmed
Santella,
The role of calcium in the cell cycle: facts and hypotheses.
1998,
Pubmed
Sirois,
The TASK-1 two-pore domain K+ channel is a molecular substrate for neuronal effects of inhalation anesthetics.
2000,
Pubmed
Skryma,
Potassium conductance in the androgen-sensitive prostate cancer cell line, LNCaP: involvement in cell proliferation.
1997,
Pubmed
Talley,
Modulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) potassium channels: volatile anesthetics and neurotransmitters share a molecular site of action.
2002,
Pubmed
Wang,
HERG K+ channel, a regulator of tumor cell apoptosis and proliferation.
2002,
Pubmed
Woodfork,
Inhibition of ATP-sensitive potassium channels causes reversible cell-cycle arrest of human breast cancer cells in tissue culture.
1995,
Pubmed
Yu,
Mediation of neuronal apoptosis by enhancement of outward potassium current.
1997,
Pubmed
Yu,
Role of the outward delayed rectifier K+ current in ceramide-induced caspase activation and apoptosis in cultured cortical neurons.
1999,
Pubmed
