Estrogen receptor alpha mediates epithelial to mesenchymal transition, expression of specific matrix effectors and functional properties of breast cancer cells
| Autor: | Spyros S. Skandalis, Panagiotis Bouris, Alexios J. Aletras, Achilleas D. Theocharis, Nikos K. Karamanos, Zoi Piperigkou, Konstantina Karamanou, Aristidis Moustakas, Nikos Afratis |
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| Rok vydání: | 2015 |
| Předmět: |
Epithelial-Mesenchymal Transition
Estrogen Receptor alpha Estrogen receptor Breast Neoplasms Transfection Biology Cell biology Extracellular Matrix Gene Expression Regulation Neoplastic Cell Movement Gene Knockdown Techniques Cancer cell MCF-7 Cells Gene silencing Humans Female Epithelial–mesenchymal transition Signal transduction skin and connective tissue diseases Estrogen receptor alpha Tyrosine kinase Molecular Biology Cell Proliferation |
| Zdroj: | Matrix biology : journal of the International Society for Matrix Biology. 43 |
| ISSN: | 1569-1802 |
| Popis: | The 17β-estradiol (E2)/estrogen receptor alpha (ERα) signaling pathway is one of the most important pathways in hormone-dependent breast cancer. E2 plays pivotal roles in cancer cell growth, survival, and architecture as well as in gene expression regulatory mechanisms. In this study, we established stably transfected MCF-7 cells by knocking down the ERα gene (designated as MCF-7/SP10+ cells), using specific shRNA lentiviral particles, and compared them with the control cells (MCF-7/c). Interestingly, ERα silencing in MCF-7 cells strongly induced cellular phenotypic changes accompanied by significant changes in gene and protein expression of several markers typical of epithelial to mesenchymal transition (EMT). Notably, these cells exhibited enhanced cell proliferation, migration and invasion. Moreover, ERα suppression strongly affected the gene and protein expression of EGFR and HER2 receptor tyrosine kinases, and various extracellular matrix (ECM) effectors, including matrix metalloproteinases and their endogenous inhibitors (MMPs/TIMPs) and components of the plasminogen activation system. The action caused by E2 in MCF-7/c cells in the expression of HER2, MT1-MMP, MMP1, MMP9, uPA, tPA, and PAI-1 was abolished in MCF-7/SP10+ cells lacking ERα. These data suggested a regulatory role for the E2/ERα pathway in respect to the composition and activity of the extracellular proteolytic molecular network. Notably, loss of ERα promoted breast cancer cell migration and invasion by inducing changes in the expression levels of certain matrix macromolecules (especially uPA, tPA, PAI-1) through the EGFR-ERK signaling pathway. In conclusion, loss of ERα in breast cancer cells results in a potent EMT characterized by striking changes in the expression profile of specific matrix macromolecules highlighting the potential nodal role of matrix effectors in breast cancer endocrine resistance. |
| Databáze: | OpenAIRE |
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