miR-145-dependent targeting of Junctional Adhesion Molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness
Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regula...
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| Veröffentlicht in: | Oncogene 2010-12, Vol.29 (50), p.6569-6580 |
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| creator | Götte, M Mohr, C Koo, C-Y Stock, C Vaske, A-K Viola, M Ibrahim, S A Peddibhotla, S Teng, Y H-F Low, J-Y Ebnet, K Kiesel, L Yip, G W |
| description | Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regulate cell motility, we aimed at investigating a potential role for miR-145 in breast cancer cell motility and invasiveness. Assisted by Affymetrix array technology, we demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to a downregulation of the cell–cell adhesion protein JAM-A and of the actin bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145 overexpression. These miR-145-dependent expression changes drastically decreased cancer cell motility, as revealed by time-lapse video microscopy, scratch wound closure assays and matrigel invasion assays. Immunofluorescence microscopy demonstrated restructuring of the actin cytoskeleton and a change in cell morphology by miR-145 overexpression, resulting in a more cortical actin distribution, and reduced actin stress fiber and filopodia formation. Nuclear rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells, accompanied by a reduction of perinuclear actin. Luciferase activation assays confirmed direct miR-145-dependent regulation of the 3′UTR of JAM-A, whereas siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. Our data provide a rationale for future miR-145-targeted approaches of antimetastatic cancer therapy. |
| doi_str_mv | 10.1038/onc.2010.386 |
| format | Article |
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In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regulate cell motility, we aimed at investigating a potential role for miR-145 in breast cancer cell motility and invasiveness. Assisted by Affymetrix array technology, we demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to a downregulation of the cell–cell adhesion protein JAM-A and of the actin bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145 overexpression. These miR-145-dependent expression changes drastically decreased cancer cell motility, as revealed by time-lapse video microscopy, scratch wound closure assays and matrigel invasion assays. Immunofluorescence microscopy demonstrated restructuring of the actin cytoskeleton and a change in cell morphology by miR-145 overexpression, resulting in a more cortical actin distribution, and reduced actin stress fiber and filopodia formation. Nuclear rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells, accompanied by a reduction of perinuclear actin. Luciferase activation assays confirmed direct miR-145-dependent regulation of the 3′UTR of JAM-A, whereas siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. Our data provide a rationale for future miR-145-targeted approaches of antimetastatic cancer therapy.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2010.386</identifier><identifier>PMID: 20818426</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>3' Untranslated regions ; 631/154/555 ; 631/337/384/331 ; 631/80/84/2336 ; 692/699/67/1347 ; Actin ; Actins - analysis ; Apoptosis ; Biological and medical sciences ; Breast cancer ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cancer cells ; Carcinoma ; Carrier Proteins - metabolism ; Cell adhesion ; Cell adhesion & migration ; Cell adhesion molecules ; Cell Adhesion Molecules - metabolism ; Cell Biology ; Cell Line, Tumor ; Cell Movement ; Cell physiology ; Cell structures and functions ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cytology ; Cytoskeleton ; Cytoskeleton, cytoplasm. Intracellular movements ; Development and progression ; Down-Regulation ; Endometrial cancer ; Endometrium ; Female ; Filopodia ; Fundamental and applied biological sciences. Psychology ; Genetic aspects ; Gynecology. Andrology. Obstetrics ; Human Genetics ; Humans ; Immunofluorescence ; Immunoglobulins - metabolism ; Internal Medicine ; Invasiveness ; Mammary gland diseases ; Medical sciences ; Medicine ; Medicine & Public Health ; Microfilament Proteins - analysis ; Microfilament Proteins - metabolism ; MicroRNA ; MicroRNAs - metabolism ; Microscopy ; Molecular and cellular biology ; Molecules ; Motility ; Muscle Proteins - analysis ; Neoplasm Invasiveness ; Oncology ; original-article ; Physiological aspects ; Plasminogen Activator Inhibitor 1 - analysis ; Receptors, Cell Surface ; Ribonucleic acid ; RNA ; Sialoglycoproteins - analysis ; siRNA ; Transcription ; Tumors ; Uterine cancer</subject><ispartof>Oncogene, 2010-12, Vol.29 (50), p.6569-6580</ispartof><rights>Macmillan Publishers Limited 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2010.</rights><rights>Copyright Nature Publishing Group Dec 16, 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-84047ea45492797c2f7637c73e1aa2dc4de5856b54bebc22886a88f2b115049f3</citedby><cites>FETCH-LOGICAL-c511t-84047ea45492797c2f7637c73e1aa2dc4de5856b54bebc22886a88f2b115049f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/onc.2010.386$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2010.386$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23706794$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20818426$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Götte, M</creatorcontrib><creatorcontrib>Mohr, C</creatorcontrib><creatorcontrib>Koo, C-Y</creatorcontrib><creatorcontrib>Stock, C</creatorcontrib><creatorcontrib>Vaske, A-K</creatorcontrib><creatorcontrib>Viola, M</creatorcontrib><creatorcontrib>Ibrahim, S A</creatorcontrib><creatorcontrib>Peddibhotla, S</creatorcontrib><creatorcontrib>Teng, Y H-F</creatorcontrib><creatorcontrib>Low, J-Y</creatorcontrib><creatorcontrib>Ebnet, K</creatorcontrib><creatorcontrib>Kiesel, L</creatorcontrib><creatorcontrib>Yip, G W</creatorcontrib><title>miR-145-dependent targeting of Junctional Adhesion Molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regulate cell motility, we aimed at investigating a potential role for miR-145 in breast cancer cell motility and invasiveness. Assisted by Affymetrix array technology, we demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to a downregulation of the cell–cell adhesion protein JAM-A and of the actin bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145 overexpression. These miR-145-dependent expression changes drastically decreased cancer cell motility, as revealed by time-lapse video microscopy, scratch wound closure assays and matrigel invasion assays. Immunofluorescence microscopy demonstrated restructuring of the actin cytoskeleton and a change in cell morphology by miR-145 overexpression, resulting in a more cortical actin distribution, and reduced actin stress fiber and filopodia formation. Nuclear rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells, accompanied by a reduction of perinuclear actin. Luciferase activation assays confirmed direct miR-145-dependent regulation of the 3′UTR of JAM-A, whereas siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. Our data provide a rationale for future miR-145-targeted approaches of antimetastatic cancer therapy.</description><subject>3' Untranslated regions</subject><subject>631/154/555</subject><subject>631/337/384/331</subject><subject>631/80/84/2336</subject><subject>692/699/67/1347</subject><subject>Actin</subject><subject>Actins - analysis</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer cells</subject><subject>Carcinoma</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell adhesion molecules</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell physiology</subject><subject>Cell structures and functions</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cytology</subject><subject>Cytoskeleton</subject><subject>Cytoskeleton, cytoplasm. Intracellular movements</subject><subject>Development and progression</subject><subject>Down-Regulation</subject><subject>Endometrial cancer</subject><subject>Endometrium</subject><subject>Female</subject><subject>Filopodia</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic aspects</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Immunoglobulins - metabolism</subject><subject>Internal Medicine</subject><subject>Invasiveness</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Microfilament Proteins - analysis</subject><subject>Microfilament Proteins - metabolism</subject><subject>MicroRNA</subject><subject>MicroRNAs - metabolism</subject><subject>Microscopy</subject><subject>Molecular and cellular biology</subject><subject>Molecules</subject><subject>Motility</subject><subject>Muscle Proteins - analysis</subject><subject>Neoplasm Invasiveness</subject><subject>Oncology</subject><subject>original-article</subject><subject>Physiological aspects</subject><subject>Plasminogen Activator Inhibitor 1 - analysis</subject><subject>Receptors, Cell Surface</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Sialoglycoproteins - analysis</subject><subject>siRNA</subject><subject>Transcription</subject><subject>Tumors</subject><subject>Uterine cancer</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqF0stu1DAUBuAIgWgp7FgjiwqxIcXX2FmOKq4qQkKwjk6ck6mrjD3YTqGvxFPidAZGQiBWjuXP59jxX1WPGT1jVJiXwdszTstMmOZOdcykbmqlWnm3OqatonXLBT-qHqR0RSnVLeX3qyNODTOSN8fVj437VDOp6gG36Af0mWSIa8zOr0kYyfvZ2-yCh4mshktM5ZN8CBPaeUKyIuAHsgnDPMGClg0jJOs8we_biOmWQ0QCKQXrIONAvrl8SSIOsy2TPiKkTCx4i5FYnKZSLrvJ5Zvb2s5fQ3LX6Euth9W9EaaEj_bjSfXl9avP52_ri49v3p2vLmqrGMu1kVRqBKlky3WrLR91I7TVAhkAH6wcUBnV9Er22FvOjWnAmJH3jCkq21GcVM93dbcxfJ0x5W7j0nI08Bjm1JlGtkq0nP1fsmIZparIp3_IqzDH8lcXpLU2jZAFnf4L8VJHUk2NOKg1TNg5P4YcwS6NuxWX5WBCKF3Ui52yMaQUcey20W0g3nSMdktuupKbbslNV3JT-JN967nf4PAb_wpKAc_2oLwvTGMsL-bSwQlNG90ud6h3LpUlv8Z4uMNfG_8E9WLZWg</recordid><startdate>20101216</startdate><enddate>20101216</enddate><creator>Götte, M</creator><creator>Mohr, C</creator><creator>Koo, C-Y</creator><creator>Stock, C</creator><creator>Vaske, A-K</creator><creator>Viola, M</creator><creator>Ibrahim, S A</creator><creator>Peddibhotla, S</creator><creator>Teng, Y H-F</creator><creator>Low, J-Y</creator><creator>Ebnet, K</creator><creator>Kiesel, L</creator><creator>Yip, G W</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20101216</creationdate><title>miR-145-dependent targeting of Junctional Adhesion Molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness</title><author>Götte, M ; 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Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Götte, M</au><au>Mohr, C</au><au>Koo, C-Y</au><au>Stock, C</au><au>Vaske, A-K</au><au>Viola, M</au><au>Ibrahim, S A</au><au>Peddibhotla, S</au><au>Teng, Y H-F</au><au>Low, J-Y</au><au>Ebnet, K</au><au>Kiesel, L</au><au>Yip, G W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-145-dependent targeting of Junctional Adhesion Molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2010-12-16</date><risdate>2010</risdate><volume>29</volume><issue>50</issue><spage>6569</spage><epage>6580</epage><pages>6569-6580</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regulate cell motility, we aimed at investigating a potential role for miR-145 in breast cancer cell motility and invasiveness. Assisted by Affymetrix array technology, we demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to a downregulation of the cell–cell adhesion protein JAM-A and of the actin bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145 overexpression. These miR-145-dependent expression changes drastically decreased cancer cell motility, as revealed by time-lapse video microscopy, scratch wound closure assays and matrigel invasion assays. Immunofluorescence microscopy demonstrated restructuring of the actin cytoskeleton and a change in cell morphology by miR-145 overexpression, resulting in a more cortical actin distribution, and reduced actin stress fiber and filopodia formation. Nuclear rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells, accompanied by a reduction of perinuclear actin. Luciferase activation assays confirmed direct miR-145-dependent regulation of the 3′UTR of JAM-A, whereas siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. Our data provide a rationale for future miR-145-targeted approaches of antimetastatic cancer therapy.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20818426</pmid><doi>10.1038/onc.2010.386</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-9232 |
| ispartof | Oncogene, 2010-12, Vol.29 (50), p.6569-6580 |
| issn | 0950-9232 1476-5594 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_864953921 |
| source | MEDLINE; SpringerLink Journals; Nature; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | 3' Untranslated regions 631/154/555 631/337/384/331 631/80/84/2336 692/699/67/1347 Actin Actins - analysis Apoptosis Biological and medical sciences Breast cancer Breast Neoplasms - metabolism Breast Neoplasms - pathology Cancer cells Carcinoma Carrier Proteins - metabolism Cell adhesion Cell adhesion & migration Cell adhesion molecules Cell Adhesion Molecules - metabolism Cell Biology Cell Line, Tumor Cell Movement Cell physiology Cell structures and functions Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cytology Cytoskeleton Cytoskeleton, cytoplasm. Intracellular movements Development and progression Down-Regulation Endometrial cancer Endometrium Female Filopodia Fundamental and applied biological sciences. Psychology Genetic aspects Gynecology. Andrology. Obstetrics Human Genetics Humans Immunofluorescence Immunoglobulins - metabolism Internal Medicine Invasiveness Mammary gland diseases Medical sciences Medicine Medicine & Public Health Microfilament Proteins - analysis Microfilament Proteins - metabolism MicroRNA MicroRNAs - metabolism Microscopy Molecular and cellular biology Molecules Motility Muscle Proteins - analysis Neoplasm Invasiveness Oncology original-article Physiological aspects Plasminogen Activator Inhibitor 1 - analysis Receptors, Cell Surface Ribonucleic acid RNA Sialoglycoproteins - analysis siRNA Transcription Tumors Uterine cancer |
| title | miR-145-dependent targeting of Junctional Adhesion Molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T00%3A53%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=miR-145-dependent%20targeting%20of%20Junctional%20Adhesion%20Molecule%20A%20and%20modulation%20of%20fascin%20expression%20are%20associated%20with%20reduced%20breast%20cancer%20cell%20motility%20and%20invasiveness&rft.jtitle=Oncogene&rft.au=G%C3%B6tte,%20M&rft.date=2010-12-16&rft.volume=29&rft.issue=50&rft.spage=6569&rft.epage=6580&rft.pages=6569-6580&rft.issn=0950-9232&rft.eissn=1476-5594&rft.coden=ONCNES&rft_id=info:doi/10.1038/onc.2010.386&rft_dat=%3Cgale_proqu%3EA245393357%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2641407083&rft_id=info:pmid/20818426&rft_galeid=A245393357&rfr_iscdi=true |