Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs.
(2009) The Journal of Cell Biology — Vol. 184, n° 3, p. 399-408 (2009)
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- 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 Snai1 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.
- Affiliations
autre University of Michigan
Citations
Rowe, R. G., Li, X.-Y., Hu, Y., Saunders, T. L., Virtanen, I., Garcia de Herreros, A., Becker, K.-F., Ingvarsen, S., Engelholm, L. H., Bommer, G., Fearon, E. R., & Weiss, S. J. (2009). Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs. The Journal of Cell Biology, 184(3), 399-408. https://doi.org/10.1083/jcb.200810113 (Original work published 2009)