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Breast Cancer Res Treat. 2017 Jun;163(3):475-484. doi: 10.1007/s10549-017-4216-6. Epub 2017 Mar 27.

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

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RECAMO, Masaryk Memorial Cancer Centre, Zluty kopec 7, 65633, Brno, Czech Republic.
Clinic of Comprehensive Cancer Care, Zluty kopec 7, 65633, Brno, Czech Republic.
RECAMO, Masaryk Memorial Cancer Centre, Zluty kopec 7, 65633, Brno, Czech Republic.
RECAMO, Masaryk Memorial Cancer Centre, Zluty kopec 7, 65633, Brno, Czech Republic.



The basal-A subtype of triple-negative breast cancer is characterized by high levels of ΔNp63. 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 ΔNp63 in basal-A triple-negative breast cancer.


Human basal-A triple-negative breast cancer cell lines with ΔNp63α 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 ΔNp63α. ΔNp63α expression increased EGFR mRNA, total EGFR protein, and phospho-EGFR(Y1086), whereas silencing endogenous ΔNp63 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 ΔNp63 alters EGFR-regulated genes involved in cell adhesion, migration, and angiogenesis. Addition of EGF or neutralizing EGFR antibodies demonstrated that EGFR activation is responsible for ΔNp63-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 ΔNp63 regulation that influences cancer cell adhesion in basal-like triple-negative breast cancer.


Adhesion; Breast cancer; EGFR; Invasion; Metastasis; p63

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