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Journal ArticleDOI

The transcription factor Snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression

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TLDR
It is shown that mouse Snail is a strong repressor of transcription of the E-cadherin gene, opening up new avenues for the design of specific anti-invasive drugs.
Abstract
The Snail family of transcription factors has previously been implicated in the differentiation of epithelial cells into mesenchymal cells (epithelial-mesenchymal transitions) during embryonic development. Epithelial-mesenchymal transitions are also determinants of the progression of carcinomas, occurring concomitantly with the cellular acquisition of migratory properties following downregulation of expression of the adhesion protein E-cadherin. Here we show that mouse Snail is a strong repressor of transcription of the E-cadherin gene. Epithelial cells that ectopically express Snail adopt a fibroblastoid phenotype and acquire tumorigenic and invasive properties. Endogenous Snail protein is present in invasive mouse and human carcinoma cell lines and tumours in which E-cadherin expression has been lost. Therefore, the same molecules are used to trigger epithelial-mesenchymal transitions during embryonic development and in tumour progression. Snail may thus be considered as a marker for malignancy, opening up new avenues for the design of specific anti-invasive drugs.

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Journal ArticleDOI

Epithelial-Mesenchymal Transitions in Development and Disease

TL;DR: The mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells

TL;DR: It is reported that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers, and it is shown that those cells have an increased ability to form mammospheres, a property associated with mammARY epithelial stem cells.
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Epithelial–mesenchymal transitions in tumour progression

TL;DR: Epithelial–mesenchymal transition provides a new basis for understanding the progression of carcinoma towards dedifferentiated and more malignant states.
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Molecular mechanisms of epithelial–mesenchymal transition

TL;DR: The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues, and the convergence of signalling pathways is essential for EMT.
Journal ArticleDOI

Snail, ZEB and bHLH factors in tumour progression: an alliance against the epithelial phenotype?

TL;DR: The identification of Snail, ZEB and some basic helix-loop-helix factors as inducers of epithelial–mesenchymal transition (EMT) and potent repressors of E-cadherin expression has opened new avenues of research with potential clinical implications.
References
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Journal ArticleDOI

Cell Adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis

TL;DR: A coupling between physical adhesion and developmental signaling provides a mechanism to tightly integrate physical aspects of tissue morphogenesis with cell growth and differentiation, a coordination that is essential to achieve the intricate patterns of cells in tissues.
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Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role

TL;DR: Evidence is provided that E-cadherin acts as an invasion suppressor molecule in epithelial tumor cell lines of dog kidney or mouse mammary gland origin.
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E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells.

TL;DR: It is suggested that the selective loss of E-cadherin expression can generate dedifferentiation and invasiveness of human carcinoma cells, and it is suggested further that E- cadher in acts as an invasion suppressor.
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Morphogenetic roles of classic cadherins

TL;DR: Classic cadherins, which are known to be crucial for homotypic cell-cell adhesion, have been found to be present not only in vertebrate but also in invertebrate species.
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An Overview of Epithelio-Mesenchymal Transformation

TL;DR: Interestingly, transfection of either metastatic cells or normal embryonic fibroblasts with the E-cadherin gene converts them to the epithelial phenotype, and it may be possible in the future to manipulate the tissue phenotype of diseased cells to the advantage of the animal.
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