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Oncogenic potential of TASK3 (Kcnk9) depends on K+channel function
Open accessAbstract
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 TASK3 G95E 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.
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Citations
Cites
Potassium channels and regulation of proliferation of human melanoma cells.
Nilius, B., & Wohlrab, W. (1992) · The Journal of Physiology · doi:10.1113/jphysiol.1992.sp018938 · Cited by 203
Cited by
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Enyedi, P., & Czirják, G. (2010) · Physiological Reviews · doi:10.1152/physrev.00029.2009 · Cited by 868
The roles of K+ channels in cancer
Pardo, L. A., & Stühmer, W. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3635 · Cited by 477
Bioelectric controls of cell proliferation: Ion channels, membrane voltage and the cell cycle
Blackiston, D. J., McLaughlin, K. A., & Levin, M. (2009) · Cell Cycle · doi:10.4161/cc.8.21.9888 · Cited by 468
Ion channels and the hallmarks of cancer
Prevarskaya, N., Skryma, R., & Shuba, Y. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.01.005 · Cited by 448
Lobikin, M., Chernet, B., Lobo, D., & Levin, M. (2012) · Physical Biology · doi:10.1088/1478-3975/9/6/065002 · Cited by 166
Metadata
- Authors
- Pei, L., Wiser, O., Slavin, A., Mu, D., Powers, S., Jan, L. Y., & Hoey, T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2003-06-02
- Volume
- 100
- Issue
- 13
- Pages
- 7803-7807
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2029179317
- Cited by
- 172
- References
- 1
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Pei, L., Wiser, O., Slavin, A., Mu, D., Powers, S., Jan, L. Y., & Hoey, T. (2003). Oncogenic potential of TASK3 (Kcnk9) depends on K+channel function. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1232448100
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
