ΔNp63 activates EGFR signaling to induce loss of adhesion in triple-negative basal-like breast cancer cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F17%3A00077851" target="_blank" >RIV/00209805:_____/17:00077851 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/content/pdf/10.1007%2Fs10549-017-4216-6.pdf" target="_blank" >https://link.springer.com/content/pdf/10.1007%2Fs10549-017-4216-6.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s10549-017-4216-6" target="_blank" >10.1007/s10549-017-4216-6</a>
Alternative languages
Result language
angličtina
Original language name
ΔNp63 activates EGFR signaling to induce loss of adhesion in triple-negative basal-like breast cancer cells
Original language description
The basal-A subtype of triple-negative breast cancer is characterized by high levels of delNp63. Various functions have been proposed for p63 in breast cancer initiation and growth, and p63 mediates chemotherapeutic response in a subset of triple-negative breast cancers. We investigated the signaling pathways that are controlled by delNp63 in basal-A triple-negative breast cancer. Human basal-A triple-negative breast cancer cell lines with delNp63a induction or inhibition were studied, along with primary human triple-negative breast cancer tissues. Proteomic, phospho-kinase array, mRNA measurements, and immunohistochemistry were employed. Global phosphoproteomics identified increased EGFR phosphorylation in MDA-MB-468 cells expressing delNp63a. delNp63a expression increased EGFR mRNA, total EGFR protein, and phospho-EGFR(Y1086), whereas silencing endogenous delNp63 in HCC1806 cells reduced both total and phospho-EGFR levels and inhibited the ability of EGF to activate EGFR. EGFR pathway gene expression analysis indicated that delNp63 alters EGFRregulated genes involved in cell adhesion, migration, and angiogenesis. Addition of EGF or neutralizing EGFR antibodies demonstrated that EGFR activation is responsible for delNp63-mediated loss of cellular adhesion. Finally, immunohistochemical staining showed that p63-positive triple-negative breast cancers were more likely to express high levels of EGFR than p63-negative cancers, corroborated by in silico analysis of gene expression profiling data. These data identify EGFR as a major target for delNp63 regulation that influences cancer cell adhesion in basal-like triple-negative breast cancer.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10601 - Cell biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Breast cancer research and treatment
ISSN
0167-6806
e-ISSN
—
Volume of the periodical
163
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
475-484
UT code for WoS article
000401465200007
EID of the result in the Scopus database
2-s2.0-85016124083