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      Voltage-Gated K + Channel, K v3.3 Is Involved in Hemin-Induced K562 Differentiation

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          Abstract

          Voltage-gated K + (K v) channels are well known to be involved in cell proliferation. However, even though cell proliferation is closely related to cell differentiation, the relationship between K v channels and cell differentiation remains poorly investigated. This study demonstrates that K v3.3 is involved in K562 cell erythroid differentiation. Down-regulation of K v3.3 using siRNA-K v3.3 increased hemin-induced K562 erythroid differentiation through decreased activation of signal molecules such as p38, cAMP response element-binding protein, and c-fos. Down-regulation of K v3.3 also enhanced cell adhesion by increasing integrin β3 and this effect was amplified when the cells were cultured with fibronectin. The K v channels, or at least K v3.3, appear to be associated with cell differentiation; therefore, understanding the mechanisms of K v channel regulation of cell differentiation would provide important information regarding vital cellular processes.

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          Most cited references49

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          Adhesion signaling - crosstalk between integrins, Src and Rho.

          Interactions between cells and the extracellular matrix coordinate signaling pathways that control various aspects of cellular behavior. Integrins sense the physical properties of the extracellular matrix and organize the cytoskeleton accordingly. In turn, this modulates signaling pathways that are triggered by various other transmembrane receptors and augments the cellular response to growth factors. Over the past years, it has become clear that there is extensive crosstalk between integrins, Src-family kinases and Rho-family GTPases at the heart of such adhesion signaling. In this Commentary, we discuss recent advances in our understanding of the dynamic regulation of the molecular connections between these three protein families. We also discuss how this signaling network can regulate a range of cellular processes that are important for normal tissue function and disease, including cell adhesion, spreading, migration and mechanotransduction.
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            Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome.

            A cell-line derived from a patient with chronic myelogenous leukemia (CML) is described. The new cell-line, which has over 175 serial passanges in a 3 1/2-yr period, has the following characteristics: (1) CML cells started to proliferate actively since they were first incubated in culture media. A threefold increase in the total number of cells was observed during the first seven passages; the cell population increased by a factor of 10 to 20 every 7 days from passage 8 through 85; from 20 to 40 times from passage 86 through 150, and more than 40 times after 150 passages. (2) The majority of the nononucleated cells are undifferentiated blasts. (3) The karyotype of all the cells examined show the Philadelphia (Ph1) chromosome and a long acrocentric marker plus aneuploidy. The Giemsa-banding studies identified the Ph1 chromosome as a terminal deletion of the long arm of chromosome 22:del(22)(q12) and the long acrocentric marker as an unbalanced reciprocal translocation of one chromosome 17 and the long arm of one chromosome 15. (4) The CML cells do not produce immunoglobulins, are free of mycoplasma, Epstein-Barr virus, and herpes-like virus particles. (5) CML cells have no alkaline phosphatase and myeloperoxidase activities and did not engulf inert particles. (6) Cultured CML cells provide a constant source of a specific antigen. This CML cell-line represents a unique source of CML cells with meaningful indicators of malignancy for clinical and experimental studies.
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              Ion channels and cancer.

              Membrane ion channels are essential for cell proliferation and appear to have a role in the development of cancer. This has initially been demonstrated for potassium channels and is meanwhile also suggested for other cation channels and Cl- channels. For some of these channels, like voltage-gated ether à go-go and Ca2+-dependent potassium channels as well as calcium and chloride channels, a cell cycle-dependent function has been demonstrated. Along with other membrane conductances, these channels control the membrane voltage and Ca2+ signaling in proliferating cells. Homeostatic parameters, such as the intracellular ion concentration, cytosolic pH and cell volume, are also governed by the activity of ion channels. Thus it will be an essential task for future studies to unravel cell cycle-specific effects of ion channels and non-specific homeostatic functions. When studying the role of ion channels in cancer cells, it is indispensable to choose experimental conditions that come close to the in vivo situation. Thus, environmental parameters, such as low oxygen pressure, acidosis and exposure to serum proteins, have to be taken into account. In order to achieve clinical application, more studies on the original cancer tissue are required, and improved animal models. Finally, it will be essential to generate more potent and specific inhibitors of ion channels to overcome the shortcomings of some of the current approaches.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 February 2016
                2016
                : 11
                : 2
                : e0148633
                Affiliations
                [001]Laboratory of Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea
                Federico II University of Naples, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MSS PDR SYL. Performed the experiments: MSS SYC. Analyzed the data: MSS SYC SYL. Wrote the paper: MSS SYL.

                Article
                PONE-D-15-26467
                10.1371/journal.pone.0148633
                4743930
                26849432
                a49b907c-b981-4e91-9ba2-534016368293
                © 2016 Song et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 June 2015
                : 20 January 2016
                Page count
                Figures: 9, Tables: 2, Pages: 19
                Funding
                This research was supported by Basic Science Research Program through National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2011-0014514, NRF-2014R1A1A3A04052757).
                Categories
                Research Article
                Biology and Life Sciences
                Developmental Biology
                Cell Differentiation
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Transfection
                Research and Analysis Methods
                Molecular Biology Techniques
                Transfection
                Biology and Life Sciences
                Cell Biology
                Cell Adhesion
                Integrins
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Extracellular Matrix
                Integrins
                Biology and Life Sciences
                Genetics
                Gene Expression
                Biology and Life Sciences
                Biochemistry
                Proteins
                Hemoglobin
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Gene Expression and Vector Techniques
                Protein Expression
                Research and Analysis Methods
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Gene Expression and Vector Techniques
                Protein Expression
                Biology and life sciences
                Cell biology
                Signal transduction
                Cell signaling
                Signaling cascades
                MAPK signaling cascades
                Biology and Life Sciences
                Cell Biology
                Cell Adhesion
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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