Dramatic dysbalancing of the Wnt pathway in breast cancers

Abstract Wnt signaling is important for breast development and remodeling during pregnancy and lactation. Epigenetic modifications change expression levels of components of the Wnt pathway, underlying oncogenic transformation. However, no clear Wnt component increasing expression universally across...

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Autores principales:	Alexey Koval, Vladimir L. Katanaev
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b8acf8efa6744abfa4f7f3b43cf6674a
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spelling	oai:doaj.org-article:b8acf8efa6744abfa4f7f3b43cf6674a2021-12-02T15:09:01ZDramatic dysbalancing of the Wnt pathway in breast cancers10.1038/s41598-018-25672-62045-2322https://doaj.org/article/b8acf8efa6744abfa4f7f3b43cf6674a2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25672-6https://doaj.org/toc/2045-2322Abstract Wnt signaling is important for breast development and remodeling during pregnancy and lactation. Epigenetic modifications change expression levels of components of the Wnt pathway, underlying oncogenic transformation. However, no clear Wnt component increasing expression universally across breast cancer (BC) or its most Wnt-dependent triple-negative BC (TNBC) subgroup has been identified, delaying development of targeted therapies. Here we perform network correlation analysis of expression of >100 Wnt pathway components in hundreds of healthy and cancerous breast tissues. Varying in expression levels among people, Wnt components remarkably coordinate their production; this coordination is dramatically decreased in BC. Clusters with coordinated gene expression exist within the healthy cohort, highlighting Wnt signaling subtypes. Different BC subgroups are identified, characterized by different remaining Wnt signaling signatures, providing the rational for patient stratification for personalizing the therapeutic applications. Key pairwise interactions within the Wnt pathway (some inherited and some established de novo) emerge as targets for future drug discovery against BC.Alexey KovalVladimir L. KatanaevNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexey Koval Vladimir L. Katanaev Dramatic dysbalancing of the Wnt pathway in breast cancers
description	Abstract Wnt signaling is important for breast development and remodeling during pregnancy and lactation. Epigenetic modifications change expression levels of components of the Wnt pathway, underlying oncogenic transformation. However, no clear Wnt component increasing expression universally across breast cancer (BC) or its most Wnt-dependent triple-negative BC (TNBC) subgroup has been identified, delaying development of targeted therapies. Here we perform network correlation analysis of expression of >100 Wnt pathway components in hundreds of healthy and cancerous breast tissues. Varying in expression levels among people, Wnt components remarkably coordinate their production; this coordination is dramatically decreased in BC. Clusters with coordinated gene expression exist within the healthy cohort, highlighting Wnt signaling subtypes. Different BC subgroups are identified, characterized by different remaining Wnt signaling signatures, providing the rational for patient stratification for personalizing the therapeutic applications. Key pairwise interactions within the Wnt pathway (some inherited and some established de novo) emerge as targets for future drug discovery against BC.
format	article
author	Alexey Koval Vladimir L. Katanaev
author_facet	Alexey Koval Vladimir L. Katanaev
author_sort	Alexey Koval
title	Dramatic dysbalancing of the Wnt pathway in breast cancers
title_short	Dramatic dysbalancing of the Wnt pathway in breast cancers
title_full	Dramatic dysbalancing of the Wnt pathway in breast cancers
title_fullStr	Dramatic dysbalancing of the Wnt pathway in breast cancers
title_full_unstemmed	Dramatic dysbalancing of the Wnt pathway in breast cancers
title_sort	dramatic dysbalancing of the wnt pathway in breast cancers
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/b8acf8efa6744abfa4f7f3b43cf6674a
work_keys_str_mv	AT alexeykoval dramaticdysbalancingofthewntpathwayinbreastcancers AT vladimirlkatanaev dramaticdysbalancingofthewntpathwayinbreastcancers
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Dramatic dysbalancing of the Wnt pathway in breast cancers

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