title: Estrogen promotes reversible epithelial-to-mesenchymal-like transition and collective motility in MCF-7 breast cancer cells.
abstract: The role of estrogen in the motility and invasion of breast cancer cells is controversial. Although estrogen receptor (ER)-positive breast tumors are considered less aggressive and more differentiated they still undergo metastasis. In many types of epithelial cancers, the ability to undergo metastasis has been associated with a loss of epithelial features and acquisition of mesenchymal properties leading to migration of individual cells, a process known as epithelial-to-mesenchymal transition (EMT). In this report, we show that a subset of ER-positive breast cancer cells can acquire mesenchymal-like features and motility in a reversible manner. In MCF-7 breast cancer cells estrogen-promoted acquisition of mesenchymal-like features while antiestrogens, such as tamoxifen, prevented this transition. Moreover, pharmacological inhibition of Src family kinases decreased the ability of estrogen to promote epithelial-to-mesenchymal-like transition. In addition to mesenchymal-like motility, a subset of estrogen-treated cells also moved as cell clusters (collective motility). While membrane localization of E-cadherin/beta-catenin was decreased in fibroblast-like cells, enhanced levels of E-cadherin/beta-catenin were detected in motile cell clusters. Thus, during tumor progression, estrogen may foster motility and invasion of ER-positive breast cancer by promoting simultaneously reversible EMT-like changes and collective motility. These studies suggest that antiestrogen therapy and Src family kinase inhibitors may decrease development of metastases in ER-positive breast cancer by blocking estrogen-dependent migration of human breast cancer cells.
authors.affiliation: Department of Pharmacology, Penn State College of Medicine, 500 University Drive, MCH078, Hershey, PA 17033, USA. mcplanas@psu.edu
authors.forename: Maricarmen D
authors.initials: MD
authors.lastname: Planas-Silva
authors.forename: Paul K
authors.initials: PK
authors.lastname: Waltz
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008648:Mesoderm / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015820:Cadherins; D004967:Estrogens; D011960:Receptors, Estrogen; D051176:beta Catenin; D013629:Tamoxifen