The Molecular Mechanisms Underlying the ERα-36-mediated Signaling in Breast Cancer

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2016 Dec 13

PMID 27941878

Citations 27

Authors

S Omarjee

J Jacquemetton

C Poulard

N Rochel

A Dejaegere

Y Chebaro

I Treilleux

E Marangoni

L Corbo

M Le Romancer

Affiliations

Soon will be listed here.

Abstract

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.

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