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Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs
- Source :
- The Journal of Cell Biology. Feb 9, 2009, Vol. 184 Issue 3, p399, 10 p.
- Publication Year :
- 2009
-
Abstract
- Epithelial-mesenchymal transition (EMT) is required for mesodermal differentiation during development. The zinc-finger transcription factor, Snail1, can trigger EMT and is sufficient to transcriptionally reprogram epithelial cells toward a mesenchymal phenotype during neoplasia and fibrosis. Whether Snail1 also regulates the behavior of terminally differentiated mesenchymal cells remains unexplored. Using a Snail conditional knockout model, we now identify Snail1 as a regulator of normal mesenchymal cell function. Snail1 expression in normal fibroblasts can be induced by agonists known to promote proliferation and invasion in vivo. When challenged within a tissue-like, three-dimensional extracellular matrix, Snail1-deficient fibroblasts exhibit global alterations in gene expression, which include defects in membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invasive activity. Snail1-deficient fibroblasts explanted atop the live chick chorioallantoic membrane lack tissue-invasive potential and fail to induce angiogenesis. These findings establish key functions for the EMT regulator Snail1 after terminal differentiation of mesenchymal cells.
Details
- Language :
- English
- ISSN :
- 00219525
- Volume :
- 184
- Issue :
- 3
- Database :
- Gale General OneFile
- Journal :
- The Journal of Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.194427823