ΔNp63 activates EGFR signaling to induce loss of adhesion in triple-negative basal-like breast cancer cells

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

ΔNp63 activates EGFR signaling to induce loss of adhesion in triple-negative basal-like breast cancer cells

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

ΔNp63 activates EGFR signaling to induce loss of adhesion in triple-negative basal-like breast cancer cells

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Breast cancer research and treatment

ISSN

0167-6806

e-ISSN

—

Svazek periodika

163

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

475-484

Kód UT WoS článku

000401465200007

EID výsledku v databázi Scopus

2-s2.0-85016124083