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Cell Rep. 2014 Sep 25;8(6):1714-1721. doi: 10.1016/j.celrep.2014.07.044. Epub 2014 Sep 15.

Transmembrane domain targeting peptide antagonizing ErbB2/Neu inhibits breast tumor growth and metastasis.

Author information

1
INSERM U 1109, Labex Medalis, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg University, Strasbourg 67200, France; CNRS UMR 7178, Institut Pluridisciplinaire Hubert Curien, Strasbourg University, Strasbourg 67037, France.
2
CNRS LISM UMR 7255, Aix Marseille University, Marseille 13402, France.
3
INSERM U 1109, Labex Medalis, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg University, Strasbourg 67200, France.
4
CNRS UPR 4301, Centre de Biophysique Moléculaire (CBM), Orleans University, Orleans F-45071, France.
5
CNRS UPR 4301, Centre de Biophysique Moléculaire (CBM), Orleans University, Orleans F-45071, France; ICOA UMR 7311, Orleans University, Orleans 45100, France.
6
CNRS UMR 7178, Institut Pluridisciplinaire Hubert Curien, Strasbourg University, Strasbourg 67037, France.
7
INSERM U 1109, Labex Medalis, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg University, Strasbourg 67200, France. Electronic address: bagnard@unistra.fr.

Abstract

Breast cancer is still a deadly disease despite major achievements in targeted therapies designed to block ligands or ligand-binding subunits of major tyrosine kinase receptors. Relapse is significant and metastases deleterious, which demands novel strategies for fighting this disease. Here, we report a proof-of-concept experiment demonstrating that small peptides interfering with the transmembrane domain of the tyrosine kinase epidermal growth factor receptor ErbB2 exhibit anticancer properties when used at micromolar dosages in a genetically engineered mouse model of breast cancer. Different assays demonstrate the specificity of the ErbB2-targeting peptide, which induces long-term reduction of ErbB2 phosphorylation and Akt signaling consistent with reduced tumor cell proliferation and increased survival. Microcomputed tomography analysis established the antimetastatic activity of the peptide and its impact on primary tumor growth. This reveals the interior of the cell membrane as an unexplored dimension for drug design.

PMID:
25220456
DOI:
10.1016/j.celrep.2014.07.044
[Indexed for MEDLINE]
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