Estrogen Receptor ß-Mediated Inhibition of Actin-Based Cell Migration Suppresses Metastasis of Inflammatory Breast Cancer.
Cancer Res
; 81(9): 2399-2414, 2021 05 01.
Article
em En
| MEDLINE
| ID: mdl-33514514
ABSTRACT
Inflammatory breast cancer (IBC) is a highly metastatic breast carcinoma with high frequency of estrogen receptor α (ERα) negativity. Here we explored the role of the second ER subtype, ERß, and report expression in IBC tumors and its correlation with reduced metastasis. Ablation of ERß in IBC cells promoted cell migration and activated gene networks that control actin reorganization, including G-protein-coupled receptors and downstream effectors that activate Rho GTPases. Analysis of preclinical mouse models of IBC revealed decreased metastasis of IBC tumors when ERß was expressed or activated by chemical agonists. Our findings support a tumor-suppressive role of ERß by demonstrating the ability of the receptor to inhibit dissemination of IBC cells and prevent metastasis. On the basis of these findings, we propose ERß as a potentially novel biomarker and therapeutic target that can inhibit IBC metastasis and reduce its associated mortality. SIGNIFICANCE:
These findings demonstrate the capacity of ERß to elicit antimetastatic effects in highly aggressive inflammatory breast cancer and propose ERß and the identified associated genes as potential therapeutic targets in this disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Movimento Celular
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Actinas
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Receptor beta de Estrogênio
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Neoplasias Inflamatórias Mamárias
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2021
Tipo de documento:
Article