Wnt pathway activity in breast cancer sub-types and stem-like cells
Wnt signalling has been implicated in stem cell regulation however its role in breast cancer stem cell regulation remains unclear. We used a panel of normal and breast cancer cell lines to assess Wnt pathway gene and protein expression, and for the investigation of Wnt signalling within stem cell-en...
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| description | Wnt signalling has been implicated in stem cell regulation however its role in breast cancer stem cell regulation remains unclear.
We used a panel of normal and breast cancer cell lines to assess Wnt pathway gene and protein expression, and for the investigation of Wnt signalling within stem cell-enriched populations, mRNA and protein expression was analysed after the selection of anoikis-resistant cells. Finally, cell lines and patient-derived samples were used to investigate Wnt pathway effects on stem cell activity in vitro.
Wnt pathway signalling increased in cancer compared to normal breast and in both cell lines and patient samples, expression of Wnt pathway genes correlated with estrogen receptor (ER) expression. Furthermore, specific Wnt pathway genes were predictive for recurrence within subtypes of breast cancer. Canonical Wnt pathway genes were increased in breast cancer stem cell-enriched populations in comparison to normal breast stem cell-enriched populations. Furthermore in cell lines, the ligand Wnt3a increased whilst the inhibitor DKK1 reduced mammosphere formation with the greatest inhibitory effects observed in ER+ve breast cancer cell lines. In patient-derived metastatic breast cancer samples, only ER-ve mammospheres were responsive to the ligand Wnt3a. However, the inhibitor DKK1 efficiently inhibited both ER+ve and ER-ve breast cancer but not normal mammosphere formation, suggesting that the Wnt pathway is aberrantly activated in breast cancer mammospheres.
Collectively, these data highlight differential Wnt signalling in breast cancer subtypes and activity in patient-derived metastatic cancer stem-like cells indicating a potential for Wnt-targeted treatment in breast cancers. |
| doi_str_mv | 10.1371/journal.pone.0067811 |
| format | Article |
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We used a panel of normal and breast cancer cell lines to assess Wnt pathway gene and protein expression, and for the investigation of Wnt signalling within stem cell-enriched populations, mRNA and protein expression was analysed after the selection of anoikis-resistant cells. Finally, cell lines and patient-derived samples were used to investigate Wnt pathway effects on stem cell activity in vitro.
Wnt pathway signalling increased in cancer compared to normal breast and in both cell lines and patient samples, expression of Wnt pathway genes correlated with estrogen receptor (ER) expression. Furthermore, specific Wnt pathway genes were predictive for recurrence within subtypes of breast cancer. Canonical Wnt pathway genes were increased in breast cancer stem cell-enriched populations in comparison to normal breast stem cell-enriched populations. Furthermore in cell lines, the ligand Wnt3a increased whilst the inhibitor DKK1 reduced mammosphere formation with the greatest inhibitory effects observed in ER+ve breast cancer cell lines. In patient-derived metastatic breast cancer samples, only ER-ve mammospheres were responsive to the ligand Wnt3a. However, the inhibitor DKK1 efficiently inhibited both ER+ve and ER-ve breast cancer but not normal mammosphere formation, suggesting that the Wnt pathway is aberrantly activated in breast cancer mammospheres.
Collectively, these data highlight differential Wnt signalling in breast cancer subtypes and activity in patient-derived metastatic cancer stem-like cells indicating a potential for Wnt-targeted treatment in breast cancers.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0067811</identifier><identifier>PMID: 23861811</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Anoikis ; Biology ; Biotechnology ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cancer ; Carcinoma, Ductal, Breast - genetics ; Carcinoma, Ductal, Breast - metabolism ; Carcinoma, Ductal, Breast - pathology ; Carcinoma, Lobular - genetics ; Carcinoma, Lobular - metabolism ; Carcinoma, Lobular - pathology ; Cell Line, Tumor ; Comparative analysis ; Dkk1 protein ; Enrichment ; Estrogen receptors ; Estrogens ; Ethics ; Female ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes ; Health aspects ; Humans ; Inhibitors ; Intercellular Signaling Peptides and Proteins - genetics ; Intercellular Signaling Peptides and Proteins - metabolism ; Medical prognosis ; Medical research ; Medicine ; Metastases ; Metastasis ; mRNA ; Neoplasm Metastasis ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Organ Specificity ; Patients ; Populations ; Proteins ; Receptors, Estrogen - genetics ; Receptors, Estrogen - metabolism ; Rodents ; Signal Transduction ; Signaling ; Stem cells ; Tumor cell lines ; Tumors ; Wnt protein ; Wnt3A Protein - genetics ; Wnt3A Protein - metabolism</subject><ispartof>PloS one, 2013-07, Vol.8 (7), p.e67811-e67811</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Lamb et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>2013 Lamb et al 2013 Lamb et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-fa95e45a27af552ea61840d07110401fbef3cd17b46fd7a43b060fbe5f3537643</citedby><cites>FETCH-LOGICAL-c758t-fa95e45a27af552ea61840d07110401fbef3cd17b46fd7a43b060fbe5f3537643</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/PMC3701602/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701602/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23861811$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Aziz, Syed A.</contributor><creatorcontrib>Lamb, Rebecca</creatorcontrib><creatorcontrib>Ablett, Matthew P</creatorcontrib><creatorcontrib>Spence, Katherine</creatorcontrib><creatorcontrib>Landberg, Göran</creatorcontrib><creatorcontrib>Sims, Andrew H</creatorcontrib><creatorcontrib>Clarke, Robert B</creatorcontrib><title>Wnt pathway activity in breast cancer sub-types and stem-like cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Wnt signalling has been implicated in stem cell regulation however its role in breast cancer stem cell regulation remains unclear.
We used a panel of normal and breast cancer cell lines to assess Wnt pathway gene and protein expression, and for the investigation of Wnt signalling within stem cell-enriched populations, mRNA and protein expression was analysed after the selection of anoikis-resistant cells. Finally, cell lines and patient-derived samples were used to investigate Wnt pathway effects on stem cell activity in vitro.
Wnt pathway signalling increased in cancer compared to normal breast and in both cell lines and patient samples, expression of Wnt pathway genes correlated with estrogen receptor (ER) expression. Furthermore, specific Wnt pathway genes were predictive for recurrence within subtypes of breast cancer. Canonical Wnt pathway genes were increased in breast cancer stem cell-enriched populations in comparison to normal breast stem cell-enriched populations. Furthermore in cell lines, the ligand Wnt3a increased whilst the inhibitor DKK1 reduced mammosphere formation with the greatest inhibitory effects observed in ER+ve breast cancer cell lines. In patient-derived metastatic breast cancer samples, only ER-ve mammospheres were responsive to the ligand Wnt3a. However, the inhibitor DKK1 efficiently inhibited both ER+ve and ER-ve breast cancer but not normal mammosphere formation, suggesting that the Wnt pathway is aberrantly activated in breast cancer mammospheres.
Collectively, these data highlight differential Wnt signalling in breast cancer subtypes and activity in patient-derived metastatic cancer stem-like cells indicating a potential for Wnt-targeted treatment in breast cancers.</description><subject>Aberration</subject><subject>Anoikis</subject><subject>Biology</subject><subject>Biotechnology</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Carcinoma, Ductal, Breast - genetics</subject><subject>Carcinoma, Ductal, Breast - metabolism</subject><subject>Carcinoma, Ductal, Breast - pathology</subject><subject>Carcinoma, Lobular - genetics</subject><subject>Carcinoma, Lobular - metabolism</subject><subject>Carcinoma, Lobular - pathology</subject><subject>Cell Line, Tumor</subject><subject>Comparative analysis</subject><subject>Dkk1 protein</subject><subject>Enrichment</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Ethics</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Inhibitors</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>mRNA</subject><subject>Neoplasm Metastasis</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Organ Specificity</subject><subject>Patients</subject><subject>Populations</subject><subject>Proteins</subject><subject>Receptors, Estrogen - genetics</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Stem cells</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><subject>Wnt protein</subject><subject>Wnt3A Protein - genetics</subject><subject>Wnt3A Protein - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1v0zAUhiMEYmPwDxBEQkJwkWLHX8kN0lQNqDRpEp-X1onjtC6pXWxnrP8el2ZTg3aBfGHr-Dnv8Tl-s-w5RjNMBH63doO30M-2zuoZQlxUGD_ITnFNyoKXiDw8Op9kT0JYI8RIxfnj7KRMO078aTb_YWO-hbj6DbscVDTXJu5yY_PGawgxV2CV9nkYmiLutjrkYNs8RL0pevNT50r3fXiaPeqgD_rZuJ9l3z5cfJ1_Ki6vPi7m55eFEqyKRQc105RBKaBjrNSQnkBRiwTGiCLcNbojqsWiobxrBVDSII5SlHWEEcEpOcteHnS3vQty7D9ITGpKK8ZrkojFgWgdrOXWmw34nXRg5N-A80sJPhrVa1mxpK44KF5WNI2iEV1JOSfAoSbA9tXej9WGZqNbpW300E9EpzfWrOTSXUsiEOaoTAJvRgHvfg06RLkxYT8wsNoN6d2paVSXtBIJffUPen93I7WE1ICxnUt11V5UnlNR0bKqMEvU7B4qrVZvjEpm6UyKTxLeThISE_VNXMIQglx8-fz_7NX3Kfv6iF1p6OMquH6IxtkwBekBVN6F4HV3N2SM5N7rt9OQe6_L0esp7cXxB90l3Zqb_AGn2vc0</recordid><startdate>20130704</startdate><enddate>20130704</enddate><creator>Lamb, Rebecca</creator><creator>Ablett, Matthew P</creator><creator>Spence, Katherine</creator><creator>Landberg, Göran</creator><creator>Sims, Andrew H</creator><creator>Clarke, Robert B</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>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>20130704</creationdate><title>Wnt pathway activity in breast cancer sub-types and stem-like cells</title><author>Lamb, Rebecca ; Ablett, Matthew P ; Spence, Katherine ; Landberg, Göran ; Sims, Andrew H ; Clarke, Robert B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-fa95e45a27af552ea61840d07110401fbef3cd17b46fd7a43b060fbe5f3537643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aberration</topic><topic>Anoikis</topic><topic>Biology</topic><topic>Biotechnology</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer</topic><topic>Carcinoma, Ductal, Breast - genetics</topic><topic>Carcinoma, Ductal, Breast - metabolism</topic><topic>Carcinoma, Ductal, Breast - pathology</topic><topic>Carcinoma, Lobular - genetics</topic><topic>Carcinoma, Lobular - metabolism</topic><topic>Carcinoma, Lobular - pathology</topic><topic>Cell Line, Tumor</topic><topic>Comparative analysis</topic><topic>Dkk1 protein</topic><topic>Enrichment</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Ethics</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Inhibitors</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>mRNA</topic><topic>Neoplasm Metastasis</topic><topic>Neoplastic Stem Cells - 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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>Lamb, Rebecca</au><au>Ablett, Matthew P</au><au>Spence, Katherine</au><au>Landberg, Göran</au><au>Sims, Andrew H</au><au>Clarke, Robert B</au><au>Aziz, Syed A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Wnt pathway activity in breast cancer sub-types and stem-like cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-07-04</date><risdate>2013</risdate><volume>8</volume><issue>7</issue><spage>e67811</spage><epage>e67811</epage><pages>e67811-e67811</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Wnt signalling has been implicated in stem cell regulation however its role in breast cancer stem cell regulation remains unclear.
We used a panel of normal and breast cancer cell lines to assess Wnt pathway gene and protein expression, and for the investigation of Wnt signalling within stem cell-enriched populations, mRNA and protein expression was analysed after the selection of anoikis-resistant cells. Finally, cell lines and patient-derived samples were used to investigate Wnt pathway effects on stem cell activity in vitro.
Wnt pathway signalling increased in cancer compared to normal breast and in both cell lines and patient samples, expression of Wnt pathway genes correlated with estrogen receptor (ER) expression. Furthermore, specific Wnt pathway genes were predictive for recurrence within subtypes of breast cancer. Canonical Wnt pathway genes were increased in breast cancer stem cell-enriched populations in comparison to normal breast stem cell-enriched populations. Furthermore in cell lines, the ligand Wnt3a increased whilst the inhibitor DKK1 reduced mammosphere formation with the greatest inhibitory effects observed in ER+ve breast cancer cell lines. In patient-derived metastatic breast cancer samples, only ER-ve mammospheres were responsive to the ligand Wnt3a. However, the inhibitor DKK1 efficiently inhibited both ER+ve and ER-ve breast cancer but not normal mammosphere formation, suggesting that the Wnt pathway is aberrantly activated in breast cancer mammospheres.
Collectively, these data highlight differential Wnt signalling in breast cancer subtypes and activity in patient-derived metastatic cancer stem-like cells indicating a potential for Wnt-targeted treatment in breast cancers.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23861811</pmid><doi>10.1371/journal.pone.0067811</doi><tpages>e67811</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1394485693 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aberration Anoikis Biology Biotechnology Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Cancer Carcinoma, Ductal, Breast - genetics Carcinoma, Ductal, Breast - metabolism Carcinoma, Ductal, Breast - pathology Carcinoma, Lobular - genetics Carcinoma, Lobular - metabolism Carcinoma, Lobular - pathology Cell Line, Tumor Comparative analysis Dkk1 protein Enrichment Estrogen receptors Estrogens Ethics Female Gene expression Gene Expression Profiling Gene Expression Regulation, Neoplastic Genes Health aspects Humans Inhibitors Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - metabolism Medical prognosis Medical research Medicine Metastases Metastasis mRNA Neoplasm Metastasis Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Organ Specificity Patients Populations Proteins Receptors, Estrogen - genetics Receptors, Estrogen - metabolism Rodents Signal Transduction Signaling Stem cells Tumor cell lines Tumors Wnt protein Wnt3A Protein - genetics Wnt3A Protein - metabolism |
| title | Wnt pathway activity in breast cancer sub-types and stem-like cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T15%3A17%3A14IST&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=Wnt%20pathway%20activity%20in%20breast%20cancer%20sub-types%20and%20stem-like%20cells&rft.jtitle=PloS%20one&rft.au=Lamb,%20Rebecca&rft.date=2013-07-04&rft.volume=8&rft.issue=7&rft.spage=e67811&rft.epage=e67811&rft.pages=e67811-e67811&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0067811&rft_dat=%3Cgale_plos_%3EA478428815%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=1394485693&rft_id=info:pmid/23861811&rft_galeid=A478428815&rft_doaj_id=oai_doaj_org_article_85060c6ac6284811b7f24663a6a93a54&rfr_iscdi=true |