Dramatic dysbalancing of the Wnt pathway in breast cancers
| Autor: | Vladimir L. Katanaev, Alexey Koval |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Science Breast Neoplasms Triple Negative Breast Neoplasms 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 Biology Article 03 medical and health sciences Breast cancer Gene expression medicine Epigenetics Wnt Signaling Pathway Breast development Multidisciplinary Cell growth Drug discovery Wnt signaling pathway medicine.disease Frizzled Receptors Wnt Proteins 030104 developmental biology Correlation analysis Cancer research Medicine |
| Zdroj: | Scientific Reports, Vol. 8, No 1 (2018) P. 7329 Scientific reports, vol. 8, no. 1, pp. 7329 Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|