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      Voltage-gated K + channels promote BT-474 breast cancer cell migration

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          A variety of ion channels have been implicated in breast cancer proliferation and metastasis. Voltage-gated K + (Kv) channels not only cause repolarization in excitable cells, but are also involved in multiple cellular functions in non-excitable cells. In this study we investigated the role of Kv channels in migration of BT474 breast cancer cells.

          Methods

          Transwell technique was used to separate migratory cells from non-migratory ones and these two groups of cells were subject to electrophysiological examinations and microfluorimetric measurements for cytosolic Ca 2+. Cell migration was examined in the absence or presence of Kv channel blockers.

          Results

          When compared with non-migratory cells, migratory cells had much higher Kv current densities, but rather unexpectedly, more depolarized membrane potential and reduced Ca 2+ influx. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the presence of Kv1.1, Kv1.3, Kv1.5, Kv2.1, Kv3.3, Kv3.4 and Kv4.3 channels. Cell migration was markedly inhibited by tetraethylammonium (TEA), a delayed rectifier Kv channel blocker, but not by 4-aminopyridine, an A-type Kv channel blocker.

          Conclusions

          Taken together, our results show that increased Kv channel expression played a role in BT474 cell migration, and Kv channels could be considered as biomarkers or potential therapeutic targets for breast cancer metastasis. The mechanism(s) by which Kv channels enhanced migration appeared unrelated to membrane hyperpolarization and Ca 2+ influx.

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          Most cited references 32

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          Orai1 and STIM1 are critical for breast tumor cell migration and metastasis.

          Tumor metastasis is the primary cause of death of cancer patients. Understanding the molecular mechanisms underlying tumor metastasis will provide potential drug targets. We report here that Orai1 and STIM1, both of which are involved in store-operated calcium entry, are essential for breast tumor cell migration in vitro and tumor metastasis in mice. Reduction of Orai1 or STIM1 by RNA interference in highly metastatic human breast cancer cells or treatment with a pharmacological inhibitor of store-operated calcium channels decreased tumor metastasis in animal models. Our data demonstrate a role for Orai1 and STIM1 in tumor metastasis and suggest store-operated calcium entry channels as potential cancer therapeutic targets.
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            miR-21 plays a pivotal role in gastric cancer pathogenesis and progression.

            Gastric cancer causes nearly one million deaths worldwide per year. Although Helicobacter pylori infection is the main risk factor, in about 80% or more of gastric cancers, the molecular pathway underlying H. pylori infection leading to the development of gastric cancers remains unclear. Recently accumulating evidence suggests that microRNAs (miRNAs) may regulate diverse biological processes and may be important in tumorigenesis. miR-21 has been frequently observed to be aberrantly overexpressed in various tumors. Using TaqMan quantitative real-time PCR, we confirmed that miR-21 was significantly overexpressed in human gastric cancer tissues and cell lines. Remarkably, miR-21 was also significantly overexpressed in H. pylori-infected gastric mucosa, implying that overexpression of miR-21 in gastric cancer may be due in part to H. pylori infection. More importantly, we showed that forced expression of miR-21 significantly enhanced cell proliferation and invasion in AGS cells, a human gastric cancer cell line, whereas knockdown of miR-21 by inhibitor caused a significant reduction in cell proliferation and a significant increase in apoptosis. Furthermore, we demonstrated that knockdown of miR-21 significantly decreased cell invasion and migration of AGS cells. Finally, we showed that RECK, a known tumor suppressor in gastric cancer, is a bona fide target of miR-21. Taken together, miR-21 may be important in the initiation and progression of gastric cancers as an oncomiR, likely through regulating RECK. Our findings suggest a potential regulatory pathway in which H. pylori infection upregulates expression of miR-21, which in turn downregulates RECK, and then leads to the development of gastric cancer.
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              The voltage-gated potassium channels and their relatives.

               Gary Yellen (2002)
              The voltage-gated potassium channels are the prototypical members of a family of membrane signalling proteins. These protein-based machines have pores that pass millions of ions per second across the membrane with astonishing selectivity, and their gates snap open and shut in milliseconds as they sense changes in voltage or ligand concentration. The architectural modules and functional components of these sophisticated signalling molecules are becoming clear, but some important links remain to be elucidated.
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                Author and article information

                Contributors
                Journal
                Chin J Cancer Res
                Chin. J. Cancer Res
                CJCR
                Chinese Journal of Cancer Research
                AME Publishing Company
                1000-9604
                1993-0631
                December 2018
                : 30
                : 6
                : 613-622
                Affiliations
                [1 ] State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau 999078, China
                [2 ] UNIMED Medical Institute, Hong Kong 999077, China
                [3 ] Organisation for Oncology and Translational Research, Hong Kong 999077, China
                [4 ] Department of Anesthesiology, China Medical University Hospital, Taichung 40447, Taiwan, China
                [5 ] Department of Anesthesiology, the Qingdao University Yuhuangding Hospital, Yantai 264000, China
                [6 ] Department of Physiology, China Medical University, Taichung 40402, Taiwan, China
                Author notes
                Prof. Louis WC Chow. Organisation for Oncology and Translational Research, Unit A, 9/F, CNT Commercial Building, 302 Queen’s Road Central, Hong Kong 999077, China. Email: lwcchow@ 123456ootr.org
                Prof. Yuk-Man Leung. Department of Physiology, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan, China. Email: ymleung@ 123456mail.cmu.edu.tw
                Article
                cjcr-30-6-613
                10.21147/j.issn.1000-9604.2018.06.06
                6328511
                Copyright © 2018 Chinese Journal of Cancer Research. All rights reserved.

                This work is licensed under a Creative Commons Attribution-Non Commercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                Categories
                Original Article

                biomarkers, migration, kv channels, breast cancer

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