The role of the voltage-gated potassium channel, Kv2.1 in prostate cancer cell migration
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Voltage-gated potassium (Kv) channels are involved in many important cellular functions and play pivotal roles in cancer progression. The expression level of Kv2.1 was observed to be higher in the highly metastatic prostate cancer cells (PC-3), specifically in their membrane, than in immortalized prostate cells (WPMY-1 cells) and comparatively less metastatic prostate cancer cells (LNCaP and DU145 cells). However, Kv2.1 expression was significantly decreased when the cells were treated with antioxidants, such as N-acetylcysteine or ascorbic acid, implying that the highly expressed Kv2.1 could detect reactive oxygen species (ROS) in malignant prostate cancer cells. In addition, the blockade of Kv2.1 with stromatoxin-1 or siRNA targeting Kv2.1 significantly inhibited the migration of malignant prostate cancer cells. Our results suggested that Kv2.1 plays an important role as a ROS sensor and that it is a promising therapeutic molecular target in metastasis of prostate cancer.
Abstract
Voltage-gated potassium (Kv) channels are involved in many important cellular functions and play pivotal roles in cancer progression. The expression level of Kv2.1 was observed to be higher in the highly metastatic prostate cancer cells (PC-3), specifically in their membrane, than in immortalized prostate cells (WPMY-1 cells) and comparatively less metastatic prostate cancer cells (LNCaP and DU145 cells). However, Kv2.1 expression was significantly decreased when the cells were treated with antioxidants, such as N-acetylcysteine or ascorbic acid, implying that the highly expressed Kv2.1 could detect reactive oxygen species (ROS) in malignant prostate cancer cells. In addition, the blockade of Kv2.1 with stromatoxin-1 or siRNA targeting Kv2.1 significantly inhibited the migration of malignant prostate cancer cells. Our results suggested that Kv2.1 plays an important role as a ROS sensor and that it is a promising therapeutic molecular target in metastasis of prostate cancer.
참고문헌 (39)
- Bertil H, "Ion channels of excitable membranes" (2001), Sinauer Associates
- Lee SY, "Adult alveolar epithelial cells express multiple subtypes of voltage-gated K+ channels that are located in apical mem-brane", Am J Physiol Cell Physiol, 284, pp.C1614~C1624 (2003)
- Pardo LA, "Voltage-gated potassium channels in cell proliferation", Physiology(Bethesda), 19, pp.285~292 (2004)
- Leanza L, "Direct phar-macological targeting of a mitochondrial ion channel sel-ectively kills tumor cells in vivo", Cancer Cell, 31, pp.516e510~531e510 (2017)
- Song MS, "Kv3. 1 and Kv3. 4, are involved in cancer cell migration and invasion", Int J Mol Sci, 19, pp.1061~ (2018)
- Johnston J, "SYMPOSIUM REVIEW : Going native : voltage‐gated potassium channels controlling neuronal excitability", J Physiol, 588, pp.3187~3200 (2010)
- Wulff H, "The voltage-gated Kv1. 3 K+ channel in effector memory T cells as new target for MS", J Clin Invest, 111, pp.1703~1713 (2003)
- Pardo LA, "Role of voltage-gated potassium channels in cancer", J Membr Biol, 205, pp.115~124 (2005)
- Szabó I, "Mitochondrial potas-sium channel Kv1. 3 mediates Bax-induced apoptosis in lymphocytes", Proc Natl Acad Sci U S A, 105, pp.14861~14866 (2008)
- Huang X, "Targeting potassium channels in cancer", J Cell Biol, 206, pp.151~162 (2014)
- Wonderlin WF, "Potassium channels, proliferation and G1 progression", J Membr Biol, 154, pp.91~107 (1996)
- Comes N, "Involve-ment of potassium channels in the progression of cancer to a more malignant phenotype", Biochim Biophys Acta, 1848, pp.2477~2492 (2015)
- 양동기, "Emerging role of transient receptor potential (TRP) channels in cancer progression", BMB Reports, 53(3), pp.125~132 (2020), 생화학분자생물학회[DOI]
- Bielanska J, "In-creased voltage-dependent K(+)channel Kv1. 3 and Kv1. 5expression correlates with leiomyosarcoma aggressiveness", Oncol Lett, 4, pp.227~230 (2012)
- Liou GY, "Reactive oxygen species in cancer", Free Radic Res, 44, pp.479~496 (2010)
- Kelly RS, "Metabolomic biomarkers of prostate cancer : pre-diction, diagnosis, progression, prognosis, and recurrence", Cancer Epidemiol Biomarkers Prev, 25, pp.887~906 (2016)
- Rigau M, "The present and future of prostate cancer urine biomarkers", Int J Mol Sci, 14, pp.12620~12649 (2013)
- Gaudreau P-O, "The present and future of biomarkers in prostate cancer : proteomics, genomics, and immunology advancements : sup-plementary issue : biomarkers and their essential role in the development of personalised therapies(A)", Biomark Cancer, 8(Suppl 2), pp.15~33 (2016)
- Lima AR, "Discrimination between the human prostate normal and cancer cell exo-metabolome by GC-MS", Sci Rep, 8, pp.1~12 (2018)
- Oto J, "A predic-tive model for prostate cancer incorporating PSA molecular forms and age", Sci Rep, 10, pp.2463~ (2020)
- Rice MA, "Biomarkers for diagnosis and prognosis of prostate cancer, Prostatectomy" (2018), IntechOpen
- Szabò I, "Contribution of voltage-gated potassium channels to the regulation of apop-tosis", FEBS Lett, 584, pp.2049~2056 (2010)
- Serrano-Novillo C, "Implication of voltage-gated potassium channels in neoplastic cell proliferation", Cancers(Basel), 11, pp.287~ (2019)
- Pardo LA, "The roles of K(+)chan-nels in cancer", Nat Rev Cancer, 14, pp.39~48 (2014)
- Jang SH, "Anti-pro-liferative effect of Kv1. 3 blockers in A549 human lung adenocarcinoma in vitro and in vivo", Eur J Pharmacol, 651, pp.26~32 (2011)
- Storz P, "Reactive oxygen species in tumor progres-sion", Front Biosci, 10, pp.1881~1896 (2005)
- Kumar B, "Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype", Cancer Res, 68, pp.1777~1785 (2008)
- Sahoo N, "Oxidative modulation of voltage-gated potassium channels", Antioxid Redox Signal, 21, pp.933~952 (2014)
- Zafarullah M, "Molecular mechanisms of N-acetylcysteine actions", Cell Mol Life Sci, 60, pp.6~20 (2003)
- Meister A, "The antioxidant effects of glutathione and ascorbic acid, oxidative stress, cell activation and viral in-fection", pp.101~111 (1994), Springer
- Lee YJ, "Suppression of human prostate cancer PC-3 cell growth by N-acetylcysteine involves over-expression of Cyr61", Toxicol In Vitro, 25, pp.199~205 (2011)
- Cho S, "Hormetic dose response to L-ascorbic acid as an anti-cancer drug in col-orectal cancer cell lines according to SVCT-2 expression", Sci Rep, 8, pp.11372~ (2018)
- Yu J, "Ion channels as potential redox sensors in lysosomes", Channels, 13, pp.477~482 (2019)
- Ogawa N, "Sensing of redox status by TRP channels", Cell Calcium, 60, pp.115~122 (2016)
- Li F, "Reciprocal regulation of actin cytoskeleton remodelling and cell mig-ration by Ca2+ and Zn2+ : role of TRPM2 channels", J Cell Sci, 129, pp.2016~2029 (2016)
- Hu X, "Hypoxic precon-ditioning enhances bone marrow mesenchymal stem cell migration via Kv2. 1 channel and FAK activation", Am J Physiol Cell Physiol, 301, pp.C362~C372 (2011)
- Subarsky P, "The hypoxic tumour micro-environment and metastatic progression", Clin Exp Metastasis, 20, pp.237~250 (2003)
- Tochhawng L, "Redox regulation of cancer cell migration and invasion", Mito-chondrion, 13, pp.246~253 (2013)
- Hurd TR, "Redox regulation of cell migration and adhesion", Trends Cell Biol, 22, pp.107~115 (2012)
