Fiche publication
Date publication
décembre 2016
Journal
Oncogene
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DEJAEGERE Annick
,
Dr ROCHEL-GUIBERTEAU Natacha
Tous les auteurs :
Omarjee S, Jacquemetton J, Poulard C, Rochel N, Dejaegere A, Chebaro Y, Treilleux I, Marangoni E, Corbo L, Le Romancer M
Lien Pubmed
Résumé
Alterations in estrogen-mediated cellular signaling have largely been implicated in the pathogenesis of breast cancer. Here, we investigated the signaling regulation of a splice variant of the estrogen receptor, namely estrogen receptor (ERα-36), associated with a poor prognosis in breast cancers. Coupling in vitro and in vivo approaches we determined the precise sequential molecular events of a new estrogen signaling network in an ERα-negative cell line and in an original patient-derived xenograft. After estrogen treatment, ERα-36 rapidly associates with Src at the level of the plasma membrane, initiating downstream cascades, including MEK1/ERK activation and paxillin phosphorylation on S126, which in turn triggers a higher expression of cyclin D1. Of note, the direct binding of ERα-36 to ERK2 prevents its dephosphorylation by MKP3 and enhances the downstream signaling. These findings improve our understanding of the regulation of non-genomic estrogen signaling and open new avenues for personalized therapeutic approaches targeting Src or MEK in ERα-36-positive patients.Oncogene advance online publication, 12 December 2016; doi:10.1038/onc.2016.415.
Référence
Oncogene. 2016 12;:
