The transcription factor snail mediates epithelial to mesenchymal transitions by repression of estrogen receptor-alpha.
Journal - Molecular endocrinology (Baltimore, Md.) (United States )
The estrogen receptor (ER)-alpha (ESR1) is a key regulatory molecule in mammary epithelial cell development. Loss of ER-alpha in breast cancer is correlated with poor prognosis, increased recurrence after treatment, and an elevated incidence of metastasis. A proposed molecular pathway by which ER-alpha acts to constrain invasive growth in breast cancer cells involves direct, ER-alpha-dependent expression of metastasis-associated protein 3, a cell-type-specific component of the Mi-2/NuRD chromatin remodeling complex. MTA3 in turn represses expression of Snail, a transcription factor linked to epithelial to mesenchymal transition and cancer metastasis. To elucidate its role(s) in epithelial to mesenchymal transition (EMT), we expressed Snail in the noninvasive, ER-alpha-positive MCF-7 cell line. Snail expression led to decreased cell-cell adhesion and increased cell invasiveness. Furthermore, we observed loss of ER-alpha expression at both the RNA and protein level that was accompanied by direct interaction of Snail with regulatory DNA sequences at the ESR1 locus. A consequence of loss of ER-alpha function in this system was the increased abundance of key components of the TGF-beta signaling pathway. Thus, cross-talk among ER-alpha, Snail, and the TGF-beta pathway appears to control critical phenotypic properties of breast cancer cells.
|ISSN : ||0888-8809|
|Mesh Heading : ||Acetylation Breast Neoplasms Cell Line, Tumor Down-Regulation Epithelial Cells Estrogen Receptor alpha Histones Humans Introns Mesenchymal Stem Cells Microarray Analysis Phenotype Promoter Regions, Genetic Protein Binding Signal Transduction Transcription Factors Transcription, Genetic Transforming Growth Factor beta metabolism genetics metabolism genetics genetics genetics genetics metabolism|
|Mesh Heading Relevant : ||Cell Differentiation cytology metabolism metabolism cytology metabolism metabolism|