Dramatic dysbalancing of the Wnt pathway in breast cancers.
Details
Serval ID
serval:BIB_6BEF7BCFE5BC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dramatic dysbalancing of the Wnt pathway in breast cancers.
Journal
Scientific reports
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
09/05/2018
Peer-reviewed
Oui
Volume
8
Number
1
Pages
7329
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
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.
Keywords
Breast Neoplasms/genetics, Breast Neoplasms/metabolism, Breast Neoplasms/physiopathology, Cell Line, Tumor, Cell Movement, Cell Proliferation, Cohort Studies, Female, Frizzled Receptors/genetics, Frizzled Receptors/metabolism, Humans, Triple Negative Breast Neoplasms/genetics, Triple Negative Breast Neoplasms/metabolism, Wnt Proteins/metabolism, Wnt Signaling Pathway/physiology
Pubmed
Web of science
Open Access
Yes
Create date
17/05/2018 18:48
Last modification date
30/04/2021 6:11