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Nat Commun. 2018 Jul 30;9(1):2980. doi: 10.1038/s41467-018-05367-2.

The actin cytoskeletal architecture of estrogen receptor positive breast cancer cells suppresses invasion.

Author information

1
Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, 85724, AZ, USA.
2
Department of Medical Oncology, Division of Molecular and Cellular Oncology, and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute and Harvard Medical School, Boston, 02115, MA, USA.
3
BioComputing Facility, University of Arizona, Tucson, 85724, AZ, USA.
4
INSERM U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, 67000, France.
5
Université de Strasbourg, Strasbourg, 67000, France.
6
Advanced Imaging Center, Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, 20147, VA, USA.
7
School of Geography and Development, College of Social and Behavioral Sciences, University of Arizona, Tucson, 85724, AZ, USA.
8
University of Arizona Cancer Center and Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, 85724, AZ, USA.
9
Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, 90048, CA, USA.
10
Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, 85724, AZ, USA. gmouneimne@email.arizona.edu.

Abstract

Estrogen promotes growth of estrogen receptor-positive (ER+) breast tumors. However, epidemiological studies examining the prognostic characteristics of breast cancer in postmenopausal women receiving hormone replacement therapy reveal a significant decrease in tumor dissemination, suggesting that estrogen has potential protective effects against cancer cell invasion. Here, we show that estrogen suppresses invasion of ER+ breast cancer cells by increasing transcription of the Ena/VASP protein, EVL, which promotes the generation of suppressive cortical actin bundles that inhibit motility dynamics, and is crucial for the ER-mediated suppression of invasion in vitro and in vivo. Interestingly, despite its benefits in suppressing tumor growth, anti-estrogenic endocrine therapy decreases EVL expression and increases local invasion in patients. Our results highlight the dichotomous effects of estrogen on tumor progression and suggest that, in contrast to its established role in promoting growth of ER+ tumors, estrogen has a significant role in suppressing invasion through actin cytoskeletal remodeling.

PMID:
30061623
PMCID:
PMC6065369
DOI:
10.1038/s41467-018-05367-2
[Indexed for MEDLINE]
Free PMC Article

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