title: Androgens Regulate T47D Cells Motility and Invasion through Actin Cytoskeleton Remodeling.
abstract: The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgen receptor (AR) is expressed in approximately 70 to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple-negative breast cancers. Recent studies have associated the actin-binding proteins of the ezrin-radixin-moesin (ERM) family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T), dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) may regulate breast cancer cell motility and invasion through the control of actin remodeling. We demonstrate that androgens promote migration and invasion in T47DviaMoesin activation. We show that T and DHEA exert their actionsviathe AR and estrogen receptor (ER), while the non-aromatizable androgen - DHT - only recruits AR. We further report that androgen induced significant changes in actin organization with pseudopodia along with membrane ruffles formation, and this process is mediated by Moesin. Our work identifies novel mechanisms of action of androgens on breast cancer cells. Through the modulation of Moesin, androgens alter the architecture of cytoskeleton in T47D breast cancer cell and promote cell migration and invasion. These results could help to understand the biological actions of androgens on breast cancer and, eventually, to develop new strategies for breast cancer treatment.
authors.affiliation: Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Clinical and Experimental Medicine, University of Pisa , Pisa , Italy.
authors.forename: Maria Magdalena
authors.initials: MM
authors.lastname: Montt-Guevara
authors.affiliation: Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Clinical and Experimental Medicine, University of Pisa , Pisa , Italy.
authors.forename: Jorge Eduardo
authors.initials: JE
authors.lastname: Shortrede
authors.affiliation: Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Clinical and Experimental Medicine, University of Pisa , Pisa , Italy.
authors.forename: Maria Silvia
authors.initials: MS
authors.lastname: Giretti
authors.affiliation: Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Clinical and Experimental Medicine, University of Pisa , Pisa , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giannini
authors.affiliation: Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Clinical and Experimental Medicine, University of Pisa , Pisa , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Mannella
authors.affiliation: Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Clinical and Experimental Medicine, University of Pisa , Pisa , Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Russo
authors.affiliation: Department of Obstetrics and Gynecology, Center for Gynecological Endocrinology, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Alessandro David
authors.initials: AD
authors.lastname: Genazzani
authors.affiliation: Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Clinical and Experimental Medicine, University of Pisa , Pisa , Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Simoncini
keywords: Moesin; actin cytoskeleton; androgens; breast cancer; metastasis