Transmembrane domain targeting peptide antagonizing ErbB2/Neu inhibits breast tumor growth and metastasis.
Fiche publication
Date publication
septembre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BAGNARD Dominique, Dr BRASSE David, Pr LAQUERRIERE Patrice, Dr OREND Gertraud
Tous les auteurs :
Arpel A, Sawma P, Spenle C, Fritz J, Meyer L, Garnier N, Velazquez-Quesada I, Hussenet T, Aci-Seche S, Baumlin N, Genest M, Brasse D, Hubert P, Cremel G, Orend G, Laquerriere P, Bagnard D
Lien Pubmed
Résumé
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.
Référence
Cell Rep. 2014 Sep 25;8(6):1714-21