Wnt pathway activity in breast cancer sub-types and stem-like cells.

<h4>Introduction</h4>Wnt signalling has been implicated in stem cell regulation however its role in breast cancer stem cell regulation remains unclear.<h4>Methods</h4>We used a panel of normal and breast cancer cell lines to assess Wnt pathway gene and protein expression, and...

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Autores principales:	Rebecca Lamb, Matthew P Ablett, Katherine Spence, Göran Landberg, Andrew H Sims, Robert B Clarke
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/85060c6ac6284811b7f24663a6a93a54
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spelling	oai:doaj.org-article:85060c6ac6284811b7f24663a6a93a542021-11-18T07:38:35ZWnt pathway activity in breast cancer sub-types and stem-like cells.1932-620310.1371/journal.pone.0067811https://doaj.org/article/85060c6ac6284811b7f24663a6a93a542013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23861811/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>Wnt signalling has been implicated in stem cell regulation however its role in breast cancer stem cell regulation remains unclear.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Rebecca LambMatthew P AblettKatherine SpenceGöran LandbergAndrew H SimsRobert B ClarkePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e67811 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rebecca Lamb Matthew P Ablett Katherine Spence Göran Landberg Andrew H Sims Robert B Clarke Wnt pathway activity in breast cancer sub-types and stem-like cells.
description	<h4>Introduction</h4>Wnt signalling has been implicated in stem cell regulation however its role in breast cancer stem cell regulation remains unclear.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
format	article
author	Rebecca Lamb Matthew P Ablett Katherine Spence Göran Landberg Andrew H Sims Robert B Clarke
author_facet	Rebecca Lamb Matthew P Ablett Katherine Spence Göran Landberg Andrew H Sims Robert B Clarke
author_sort	Rebecca Lamb
title	Wnt pathway activity in breast cancer sub-types and stem-like cells.
title_short	Wnt pathway activity in breast cancer sub-types and stem-like cells.
title_full	Wnt pathway activity in breast cancer sub-types and stem-like cells.
title_fullStr	Wnt pathway activity in breast cancer sub-types and stem-like cells.
title_full_unstemmed	Wnt pathway activity in breast cancer sub-types and stem-like cells.
title_sort	wnt pathway activity in breast cancer sub-types and stem-like cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/85060c6ac6284811b7f24663a6a93a54
work_keys_str_mv	AT rebeccalamb wntpathwayactivityinbreastcancersubtypesandstemlikecells AT matthewpablett wntpathwayactivityinbreastcancersubtypesandstemlikecells AT katherinespence wntpathwayactivityinbreastcancersubtypesandstemlikecells AT goranlandberg wntpathwayactivityinbreastcancersubtypesandstemlikecells AT andrewhsims wntpathwayactivityinbreastcancersubtypesandstemlikecells AT robertbclarke wntpathwayactivityinbreastcancersubtypesandstemlikecells
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Wnt pathway activity in breast cancer sub-types and stem-like cells.

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