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

Marco Padilla-Rodriguez, Sara S. Parker, Deanna G. Adams, Thomas Westerling, Julieann I. Puleo, Adam W. Watson, Samantha M. Hill, Muhammad Noon, Raphael Gaudin, Jesse Aaron, Daoqin Tong, Denise J. Roe, Beatrice Knudsen and Ghassan Mouneimne ()
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Marco Padilla-Rodriguez: University of Arizona
Sara S. Parker: University of Arizona
Deanna G. Adams: University of Arizona
Thomas Westerling: Dana-Farber Cancer Institute and Harvard Medical School
Julieann I. Puleo: University of Arizona
Adam W. Watson: University of Arizona
Samantha M. Hill: University of Arizona
Muhammad Noon: University of Arizona
Raphael Gaudin: Institut de Recherche sur les Maladies Virales et Hépatiques
Jesse Aaron: Howard Hughes Medical Institute
Daoqin Tong: University of Arizona
Denise J. Roe: University of Arizona
Beatrice Knudsen: Cedars-Sinai Medical Center
Ghassan Mouneimne: University of Arizona

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05367-2

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