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

<h4>Background</h4>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. M...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9a8e1dd5b75140d99a9bd3efefd3e553
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spelling	oai:doaj.org-article:9a8e1dd5b75140d99a9bd3efefd3e5532021-11-25T06:12:22ZExtra-nuclear signalling of estrogen receptor to breast cancer cytoskeletal remodelling, migration and invasion.1932-620310.1371/journal.pone.0002238https://doaj.org/article/9a8e1dd5b75140d99a9bd3efefd3e5532008-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18493596/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 results in the recruitment of the small GTPase RhoA and in the subsequent activation of its downstream effector Rho-associated kinase-2 (ROCK-2). ROCK-2 is responsible for moesin phosphorylation. The G alpha(13)/RhoA/ROCK/moesin cascade is necessary for the cytoskeletal remodeling and for the enhancement of breast cancer cell horizontal migration and invasion of three-dimensional matrices induced by estrogen. In addition, human samples of normal breast tissue, fibroadenomas and invasive ductal carcinomas show that the expression of wild-type moesin as well as of its active form is deranged in cancers, with increased protein amounts and a loss of association with the cell membrane.<h4>Conclusions/significance</h4>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.Maria Silvia GirettiXiao-Dong FuGiovanni De RosaIvana SarottoChiara BaldacciSilvia GaribaldiPaolo MannellaNicoletta BigliaPiero SismondiAndrea Riccardo GenazzaniTommaso SimonciniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 5, p e2238 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Extra-nuclear signalling of estrogen receptor to breast cancer cytoskeletal remodelling, migration and invasion.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 results in the recruitment of the small GTPase RhoA and in the subsequent activation of its downstream effector Rho-associated kinase-2 (ROCK-2). ROCK-2 is responsible for moesin phosphorylation. The G alpha(13)/RhoA/ROCK/moesin cascade is necessary for the cytoskeletal remodeling and for the enhancement of breast cancer cell horizontal migration and invasion of three-dimensional matrices induced by estrogen. In addition, human samples of normal breast tissue, fibroadenomas and invasive ductal carcinomas show that the expression of wild-type moesin as well as of its active form is deranged in cancers, with increased protein amounts and a loss of association with the cell membrane.<h4>Conclusions/significance</h4>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.
format	article
author	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
author_facet	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
author_sort	Maria Silvia Giretti
title	Extra-nuclear signalling of estrogen receptor to breast cancer cytoskeletal remodelling, migration and invasion.
title_short	Extra-nuclear signalling of estrogen receptor to breast cancer cytoskeletal remodelling, migration and invasion.
title_full	Extra-nuclear signalling of estrogen receptor to breast cancer cytoskeletal remodelling, migration and invasion.
title_fullStr	Extra-nuclear signalling of estrogen receptor to breast cancer cytoskeletal remodelling, migration and invasion.
title_full_unstemmed	Extra-nuclear signalling of estrogen receptor to breast cancer cytoskeletal remodelling, migration and invasion.
title_sort	extra-nuclear signalling of estrogen receptor to breast cancer cytoskeletal remodelling, migration and invasion.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/9a8e1dd5b75140d99a9bd3efefd3e553
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Extra-nuclear signalling of estrogen receptor to breast cancer cytoskeletal remodelling, migration and invasion.

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