Inhibition of SK4 Potassium Channels Suppresses Cell Proliferation, Migration and the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells

Treatments for triple-negative breast cancer (TNBC) are limited; intermediate-conductance calcium-activated potassium (SK4) channels are closely involved in tumor progression, but little is known about these channels in TNBC. We aimed to investigate whether SK4 channels affect TNBC. First, by immuno...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2016-04, Vol.11 (4), p.e0154471-e0154471
Hauptverfasser: Zhang, Panshi, Yang, Xiaowei, Yin, Qian, Yi, Jilin, Shen, Wenzhuang, Zhao, Lu, Zhu, Zhi, Liu, Jinwen
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page e0154471
container_issue 4
container_start_page e0154471
container_title PloS one
container_volume 11
creator Zhang, Panshi
Yang, Xiaowei
Yin, Qian
Yi, Jilin
Shen, Wenzhuang
Zhao, Lu
Zhu, Zhi
Liu, Jinwen
description Treatments for triple-negative breast cancer (TNBC) are limited; intermediate-conductance calcium-activated potassium (SK4) channels are closely involved in tumor progression, but little is known about these channels in TNBC. We aimed to investigate whether SK4 channels affect TNBC. First, by immunohistochemistry (IHC) and western blotting (WB), increased SK4 protein expression in breast tumor tissues was detected relative to that in non-tumor breast tissues, but there was no apparent expression difference between various subtypes of breast cancer (p>0.05). Next, functional SK4 channels were detected in the TNBC cell line MDA-MB-231 using WB, real-time PCR, immunofluorescence and patch-clamp recording. By employing SK4 specific siRNAs and blockers, including TRAM-34 and clotrimazole, in combination with an MTT assay, a colony-formation assay, flow cytometry and a cell motility assay, we found that the suppression of SK4 channels significantly inhibited cell proliferation and migration and promoted apoptosis in MDA-MB-231 cells (p
doi_str_mv 10.1371/journal.pone.0154471
format Article
fullrecord <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1785219828</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A453418265</galeid><doaj_id>oai_doaj_org_article_089d18138c704825867034643f963670</doaj_id><sourcerecordid>A453418265</sourcerecordid><originalsourceid>FETCH-LOGICAL-c725t-aab0ff0158970562bf3ff716fa25527d7893444509924f29bb179db05c940bec3</originalsourceid><addsrcrecordid>eNqNk11rFDEUhgdRbK3-A9FAQRTcNV8zSW6EulRdbG2x1duQmUl2UrLJmMwU-2f8rWa729KVgjIX-ZjnPefkTU5RPEdwighD7y7CGL1y0z54PYWopJShB8UuEgRPKgzJwzvzneJJShcQloRX1eNiBzOEKUJst_g9952t7WCDB8GAsy8UnIZBpWTHJZh1ynvtEjgb-z7qlHQCM-0cOI3BWaOjWunegmO7WE-B8i0YOg0Oe5sHZ5WbHOukfdNdLZUD51H5tE5mfV7Z3unJV73I4ksNPkSt0gBmyjc6XidKT4tHRrmkn23GveL7x8Pz2efJ0cmn-ezgaNIwXA4TpWpoTDaBCwbLCteGGMNQZRQuS8xaxgWhlJZQCEwNFnWNmGhrWDaCwlo3ZK94uY7bu5DkxtokEeMlRoJjnon5mmiDupB9tEsVr2RQVl5vhLiQKg62cVpCLlrEEeENg5TjklcMElpRYkRFVvO94v0m21gvddtoP0TltoJu__G2k4twKSmnorou5vUmQAw_R50GubSpyYYpr8OY6-awpIITgf-N5iOybAypMrr_F3q_ERtqofJZrTchl9isgsoDWhKKOK7KTE3vofLX6qVt8pM1Nu9vCd5sCTIz6F_DQo0pyfnZt_9nT35ss6_usJ1WbuhScOPqEaZtkK7BJoaUoja394GgXHXcjRty1XFy03FZ9uLuXd6KblqM_AGEMSUz</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1785219828</pqid></control><display><type>article</type><title>Inhibition of SK4 Potassium Channels Suppresses Cell Proliferation, Migration and the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Zhang, Panshi ; Yang, Xiaowei ; Yin, Qian ; Yi, Jilin ; Shen, Wenzhuang ; Zhao, Lu ; Zhu, Zhi ; Liu, Jinwen</creator><contributor>Ahmad, Aamir</contributor><creatorcontrib>Zhang, Panshi ; Yang, Xiaowei ; Yin, Qian ; Yi, Jilin ; Shen, Wenzhuang ; Zhao, Lu ; Zhu, Zhi ; Liu, Jinwen ; Ahmad, Aamir</creatorcontrib><description>Treatments for triple-negative breast cancer (TNBC) are limited; intermediate-conductance calcium-activated potassium (SK4) channels are closely involved in tumor progression, but little is known about these channels in TNBC. We aimed to investigate whether SK4 channels affect TNBC. First, by immunohistochemistry (IHC) and western blotting (WB), increased SK4 protein expression in breast tumor tissues was detected relative to that in non-tumor breast tissues, but there was no apparent expression difference between various subtypes of breast cancer (p&gt;0.05). Next, functional SK4 channels were detected in the TNBC cell line MDA-MB-231 using WB, real-time PCR, immunofluorescence and patch-clamp recording. By employing SK4 specific siRNAs and blockers, including TRAM-34 and clotrimazole, in combination with an MTT assay, a colony-formation assay, flow cytometry and a cell motility assay, we found that the suppression of SK4 channels significantly inhibited cell proliferation and migration and promoted apoptosis in MDA-MB-231 cells (p&lt;0.05). Further investigation revealed that treatment with epidermal growth factor (EGF)/basic fibroblast growth factor (bFGF) caused MDA-MB-231 cells to undergo the epithelial-mesenchymal transition (EMT) and to show increased SK4 mRNA expression. In addition, the down-regulation of SK4 expression inhibited the EMT markers Vimentin and Snail1. Collectively, our findings suggest that SK4 channels are expressed in TNBC and are involved in the proliferation, apoptosis, migration and EMT processes of TNBC cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0154471</identifier><identifier>PMID: 27124117</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Apoptosis ; Assaying ; Biology and Life Sciences ; Breast cancer ; Calcium ; Calcium channels ; Calcium conductance ; Cancer ; Cancer therapies ; Care and treatment ; Cell cycle ; Cell growth ; Cell Line, Tumor ; Cell migration ; Cell Movement ; Cell Proliferation ; Cell Survival ; Channels ; Chemotherapy ; Clotrimazole ; Clotrimazole - pharmacology ; Cytometry ; Epidermal growth factor ; Epithelial-Mesenchymal Transition - drug effects ; Female ; Fibroblast growth factor 2 ; Fibroblasts ; Flow cytometry ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Growth factors ; Humans ; Immunofluorescence ; Immunohistochemistry ; Intermediate-Conductance Calcium-Activated Potassium Channels - antagonists &amp; inhibitors ; Intermediate-Conductance Calcium-Activated Potassium Channels - genetics ; Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism ; MCF-7 Cells ; Medicine and Health Sciences ; Mesenchyme ; Physiology ; Potassium ; Potassium channels ; Potassium conductance ; Pyrazoles - pharmacology ; Research and Analysis Methods ; Resistance ; RNA ; Science ; siRNA ; Studies ; Surgery ; Thyroid gland ; Tissues ; Triple Negative Breast Neoplasms - genetics ; Triple Negative Breast Neoplasms - metabolism ; Triple Negative Breast Neoplasms - pathology ; Up-Regulation - drug effects ; Vimentin ; Western blotting</subject><ispartof>PloS one, 2016-04, Vol.11 (4), p.e0154471-e0154471</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Zhang et al 2016 Zhang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-aab0ff0158970562bf3ff716fa25527d7893444509924f29bb179db05c940bec3</citedby><cites>FETCH-LOGICAL-c725t-aab0ff0158970562bf3ff716fa25527d7893444509924f29bb179db05c940bec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849628/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849628/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23847,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27124117$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ahmad, Aamir</contributor><creatorcontrib>Zhang, Panshi</creatorcontrib><creatorcontrib>Yang, Xiaowei</creatorcontrib><creatorcontrib>Yin, Qian</creatorcontrib><creatorcontrib>Yi, Jilin</creatorcontrib><creatorcontrib>Shen, Wenzhuang</creatorcontrib><creatorcontrib>Zhao, Lu</creatorcontrib><creatorcontrib>Zhu, Zhi</creatorcontrib><creatorcontrib>Liu, Jinwen</creatorcontrib><title>Inhibition of SK4 Potassium Channels Suppresses Cell Proliferation, Migration and the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Treatments for triple-negative breast cancer (TNBC) are limited; intermediate-conductance calcium-activated potassium (SK4) channels are closely involved in tumor progression, but little is known about these channels in TNBC. We aimed to investigate whether SK4 channels affect TNBC. First, by immunohistochemistry (IHC) and western blotting (WB), increased SK4 protein expression in breast tumor tissues was detected relative to that in non-tumor breast tissues, but there was no apparent expression difference between various subtypes of breast cancer (p&gt;0.05). Next, functional SK4 channels were detected in the TNBC cell line MDA-MB-231 using WB, real-time PCR, immunofluorescence and patch-clamp recording. By employing SK4 specific siRNAs and blockers, including TRAM-34 and clotrimazole, in combination with an MTT assay, a colony-formation assay, flow cytometry and a cell motility assay, we found that the suppression of SK4 channels significantly inhibited cell proliferation and migration and promoted apoptosis in MDA-MB-231 cells (p&lt;0.05). Further investigation revealed that treatment with epidermal growth factor (EGF)/basic fibroblast growth factor (bFGF) caused MDA-MB-231 cells to undergo the epithelial-mesenchymal transition (EMT) and to show increased SK4 mRNA expression. In addition, the down-regulation of SK4 expression inhibited the EMT markers Vimentin and Snail1. Collectively, our findings suggest that SK4 channels are expressed in TNBC and are involved in the proliferation, apoptosis, migration and EMT processes of TNBC cells.</description><subject>Analysis</subject><subject>Apoptosis</subject><subject>Assaying</subject><subject>Biology and Life Sciences</subject><subject>Breast cancer</subject><subject>Calcium</subject><subject>Calcium channels</subject><subject>Calcium conductance</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Channels</subject><subject>Chemotherapy</subject><subject>Clotrimazole</subject><subject>Clotrimazole - pharmacology</subject><subject>Cytometry</subject><subject>Epidermal growth factor</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Female</subject><subject>Fibroblast growth factor 2</subject><subject>Fibroblasts</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Immunohistochemistry</subject><subject>Intermediate-Conductance Calcium-Activated Potassium Channels - antagonists &amp; inhibitors</subject><subject>Intermediate-Conductance Calcium-Activated Potassium Channels - genetics</subject><subject>Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism</subject><subject>MCF-7 Cells</subject><subject>Medicine and Health Sciences</subject><subject>Mesenchyme</subject><subject>Physiology</subject><subject>Potassium</subject><subject>Potassium channels</subject><subject>Potassium conductance</subject><subject>Pyrazoles - pharmacology</subject><subject>Research and Analysis Methods</subject><subject>Resistance</subject><subject>RNA</subject><subject>Science</subject><subject>siRNA</subject><subject>Studies</subject><subject>Surgery</subject><subject>Thyroid gland</subject><subject>Tissues</subject><subject>Triple Negative Breast Neoplasms - genetics</subject><subject>Triple Negative Breast Neoplasms - metabolism</subject><subject>Triple Negative Breast Neoplasms - pathology</subject><subject>Up-Regulation - drug effects</subject><subject>Vimentin</subject><subject>Western blotting</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11rFDEUhgdRbK3-A9FAQRTcNV8zSW6EulRdbG2x1duQmUl2UrLJmMwU-2f8rWa729KVgjIX-ZjnPefkTU5RPEdwighD7y7CGL1y0z54PYWopJShB8UuEgRPKgzJwzvzneJJShcQloRX1eNiBzOEKUJst_g9952t7WCDB8GAsy8UnIZBpWTHJZh1ynvtEjgb-z7qlHQCM-0cOI3BWaOjWunegmO7WE-B8i0YOg0Oe5sHZ5WbHOukfdNdLZUD51H5tE5mfV7Z3unJV73I4ksNPkSt0gBmyjc6XidKT4tHRrmkn23GveL7x8Pz2efJ0cmn-ezgaNIwXA4TpWpoTDaBCwbLCteGGMNQZRQuS8xaxgWhlJZQCEwNFnWNmGhrWDaCwlo3ZK94uY7bu5DkxtokEeMlRoJjnon5mmiDupB9tEsVr2RQVl5vhLiQKg62cVpCLlrEEeENg5TjklcMElpRYkRFVvO94v0m21gvddtoP0TltoJu__G2k4twKSmnorou5vUmQAw_R50GubSpyYYpr8OY6-awpIITgf-N5iOybAypMrr_F3q_ERtqofJZrTchl9isgsoDWhKKOK7KTE3vofLX6qVt8pM1Nu9vCd5sCTIz6F_DQo0pyfnZt_9nT35ss6_usJ1WbuhScOPqEaZtkK7BJoaUoja394GgXHXcjRty1XFy03FZ9uLuXd6KblqM_AGEMSUz</recordid><startdate>20160428</startdate><enddate>20160428</enddate><creator>Zhang, Panshi</creator><creator>Yang, Xiaowei</creator><creator>Yin, Qian</creator><creator>Yi, Jilin</creator><creator>Shen, Wenzhuang</creator><creator>Zhao, Lu</creator><creator>Zhu, Zhi</creator><creator>Liu, Jinwen</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160428</creationdate><title>Inhibition of SK4 Potassium Channels Suppresses Cell Proliferation, Migration and the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells</title><author>Zhang, Panshi ; Yang, Xiaowei ; Yin, Qian ; Yi, Jilin ; Shen, Wenzhuang ; Zhao, Lu ; Zhu, Zhi ; Liu, Jinwen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c725t-aab0ff0158970562bf3ff716fa25527d7893444509924f29bb179db05c940bec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Analysis</topic><topic>Apoptosis</topic><topic>Assaying</topic><topic>Biology and Life Sciences</topic><topic>Breast cancer</topic><topic>Calcium</topic><topic>Calcium channels</topic><topic>Calcium conductance</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Channels</topic><topic>Chemotherapy</topic><topic>Clotrimazole</topic><topic>Clotrimazole - pharmacology</topic><topic>Cytometry</topic><topic>Epidermal growth factor</topic><topic>Epithelial-Mesenchymal Transition - drug effects</topic><topic>Female</topic><topic>Fibroblast growth factor 2</topic><topic>Fibroblasts</topic><topic>Flow cytometry</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Immunofluorescence</topic><topic>Immunohistochemistry</topic><topic>Intermediate-Conductance Calcium-Activated Potassium Channels - antagonists &amp; inhibitors</topic><topic>Intermediate-Conductance Calcium-Activated Potassium Channels - genetics</topic><topic>Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism</topic><topic>MCF-7 Cells</topic><topic>Medicine and Health Sciences</topic><topic>Mesenchyme</topic><topic>Physiology</topic><topic>Potassium</topic><topic>Potassium channels</topic><topic>Potassium conductance</topic><topic>Pyrazoles - pharmacology</topic><topic>Research and Analysis Methods</topic><topic>Resistance</topic><topic>RNA</topic><topic>Science</topic><topic>siRNA</topic><topic>Studies</topic><topic>Surgery</topic><topic>Thyroid gland</topic><topic>Tissues</topic><topic>Triple Negative Breast Neoplasms - genetics</topic><topic>Triple Negative Breast Neoplasms - metabolism</topic><topic>Triple Negative Breast Neoplasms - pathology</topic><topic>Up-Regulation - drug effects</topic><topic>Vimentin</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Panshi</creatorcontrib><creatorcontrib>Yang, Xiaowei</creatorcontrib><creatorcontrib>Yin, Qian</creatorcontrib><creatorcontrib>Yi, Jilin</creatorcontrib><creatorcontrib>Shen, Wenzhuang</creatorcontrib><creatorcontrib>Zhao, Lu</creatorcontrib><creatorcontrib>Zhu, Zhi</creatorcontrib><creatorcontrib>Liu, Jinwen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Panshi</au><au>Yang, Xiaowei</au><au>Yin, Qian</au><au>Yi, Jilin</au><au>Shen, Wenzhuang</au><au>Zhao, Lu</au><au>Zhu, Zhi</au><au>Liu, Jinwen</au><au>Ahmad, Aamir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of SK4 Potassium Channels Suppresses Cell Proliferation, Migration and the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-04-28</date><risdate>2016</risdate><volume>11</volume><issue>4</issue><spage>e0154471</spage><epage>e0154471</epage><pages>e0154471-e0154471</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Treatments for triple-negative breast cancer (TNBC) are limited; intermediate-conductance calcium-activated potassium (SK4) channels are closely involved in tumor progression, but little is known about these channels in TNBC. We aimed to investigate whether SK4 channels affect TNBC. First, by immunohistochemistry (IHC) and western blotting (WB), increased SK4 protein expression in breast tumor tissues was detected relative to that in non-tumor breast tissues, but there was no apparent expression difference between various subtypes of breast cancer (p&gt;0.05). Next, functional SK4 channels were detected in the TNBC cell line MDA-MB-231 using WB, real-time PCR, immunofluorescence and patch-clamp recording. By employing SK4 specific siRNAs and blockers, including TRAM-34 and clotrimazole, in combination with an MTT assay, a colony-formation assay, flow cytometry and a cell motility assay, we found that the suppression of SK4 channels significantly inhibited cell proliferation and migration and promoted apoptosis in MDA-MB-231 cells (p&lt;0.05). Further investigation revealed that treatment with epidermal growth factor (EGF)/basic fibroblast growth factor (bFGF) caused MDA-MB-231 cells to undergo the epithelial-mesenchymal transition (EMT) and to show increased SK4 mRNA expression. In addition, the down-regulation of SK4 expression inhibited the EMT markers Vimentin and Snail1. Collectively, our findings suggest that SK4 channels are expressed in TNBC and are involved in the proliferation, apoptosis, migration and EMT processes of TNBC cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27124117</pmid><doi>10.1371/journal.pone.0154471</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2016-04, Vol.11 (4), p.e0154471-e0154471
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1785219828
source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS)
subjects Analysis
Apoptosis
Assaying
Biology and Life Sciences
Breast cancer
Calcium
Calcium channels
Calcium conductance
Cancer
Cancer therapies
Care and treatment
Cell cycle
Cell growth
Cell Line, Tumor
Cell migration
Cell Movement
Cell Proliferation
Cell Survival
Channels
Chemotherapy
Clotrimazole
Clotrimazole - pharmacology
Cytometry
Epidermal growth factor
Epithelial-Mesenchymal Transition - drug effects
Female
Fibroblast growth factor 2
Fibroblasts
Flow cytometry
Gene expression
Gene Expression Regulation, Neoplastic - drug effects
Growth factors
Humans
Immunofluorescence
Immunohistochemistry
Intermediate-Conductance Calcium-Activated Potassium Channels - antagonists & inhibitors
Intermediate-Conductance Calcium-Activated Potassium Channels - genetics
Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism
MCF-7 Cells
Medicine and Health Sciences
Mesenchyme
Physiology
Potassium
Potassium channels
Potassium conductance
Pyrazoles - pharmacology
Research and Analysis Methods
Resistance
RNA
Science
siRNA
Studies
Surgery
Thyroid gland
Tissues
Triple Negative Breast Neoplasms - genetics
Triple Negative Breast Neoplasms - metabolism
Triple Negative Breast Neoplasms - pathology
Up-Regulation - drug effects
Vimentin
Western blotting
title Inhibition of SK4 Potassium Channels Suppresses Cell Proliferation, Migration and the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T11%3A12%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibition%20of%20SK4%20Potassium%20Channels%20Suppresses%20Cell%20Proliferation,%20Migration%20and%20the%20Epithelial-Mesenchymal%20Transition%20in%20Triple-Negative%20Breast%20Cancer%20Cells&rft.jtitle=PloS%20one&rft.au=Zhang,%20Panshi&rft.date=2016-04-28&rft.volume=11&rft.issue=4&rft.spage=e0154471&rft.epage=e0154471&rft.pages=e0154471-e0154471&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0154471&rft_dat=%3Cgale_plos_%3EA453418265%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1785219828&rft_id=info:pmid/27124117&rft_galeid=A453418265&rft_doaj_id=oai_doaj_org_article_089d18138c704825867034643f963670&rfr_iscdi=true