Extra-nuclear signalling of estrogen receptor to breast cancer cytoskeletal remodelling, migration and invasion

雌激素受体的核外信号传导对乳腺癌细胞骨架重塑、迁移和侵袭的影响

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作者:Maria Silvia Giretti, Xiao-Dong Fu, Giovanni De Rosa, Ivana Sarotto, Chiara Baldacci, Silvia Garibaldi, Paolo Mannella, Nicoletta Biglia, Piero Sismondi, Andrea Riccardo Genazzani, Tommaso Simoncini

Background

Estrogen is an established enhancer of breast cancer development, but less is known on its effect on local progression or metastasis. We studied the effect of estrogen receptor recruitment on actin cytoskeleton remodeling and breast cancer cell movement and invasion. Moreover, we characterized the signaling steps through which these actions are enacted. Methodology/principal findings: In estrogen receptor (ER) positive T47-D breast cancer cells ER activation with 17beta-estradiol induces rapid and dynamic actin cytoskeleton remodeling with the formation of specialized cell membrane structures like ruffles and pseudopodia. These effects depend on the rapid recruitment of the actin-binding protein moesin. Moesin activation by estradiol depends on the interaction of ER alpha with the G protein G alpha(13), which

Significance

These results provide an original mechanism through which estrogen can facilitate breast cancer local and distant progression, identifying the extra-nuclear G alpha(13)/RhoA/ROCK/moesin signaling cascade as a target of ER alpha in breast cancer cells. This information helps to understand the effects of estrogen on breast cancer metastasis and may provide new targets for therapeutic interventions.

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